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Adult Stem Cells: The Best Kept Secret In Medicine …

By Adult Stem Cells

Stem cell therapies and their lifesaving results are arguably the best kept medical secret. Stem cells are currently being used in several thousand FDA-approved clinical trials, are treating tens of thousands of patients every year, and cumulatively over 1.5 million people have been treated to date. Yet these numbers, and the lifesaving results from stem cells for dozens of conditions, are unknown to most. Why the information blackout? Perhaps for lack of an adjective.

You see, those heartening numbers are all due to adult stem cells. Long ignored by the media and disparaged even by many in the scientific community, adult stem cells those not dependent on the destruction of embryos are the true gold standard for stem cells, especially when it comes to treating patients.

A recent New York Times piece provides a perfect example of the disinformation campaign. Early on, the author discusses the theoretical nature of stem cell treatments and bemoans the fact that progress is slow, almost all the research is still in mice or petri dishes, and The very few clinical trials that have begun are still in the earliest phase.

Whether through ignorance or bias, the sole focus is clearly on embryonic stem cells. Such writing, however, serves to confuse, not illuminate, the facts about stem cells and therapies.

Contrary to the blinkered portrayal of stem cells in the article, there are in fact almost 3,500 ongoing or completed clinical trials using adult stem cells, listed in the NIH/FDA-approved database. Moreover, large numbers of patients have been treated with adult stem cells. In 2012 there were almost 70,000 patients treated around the globe in that year alone, and almost 20,000 patients treated in just the U.S. in 2014. Cumulatively, its been documented that as of December 2012, there had already been over one million adult stem cell transplants. This means that now, over 1.5 million patients have had their lives saved and health improved by adult stem cell transplants.

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Our focus is indeed on adult stem cells both because they are efficacious for patients, as well as because adult stem cells are derived without the destruction of the stem cell donor, unlike embryonic stem cells and fetal stem cells. Both positions are based on the facts of biology.

The New York Times Kolata criticizes various stem cell clinics within the U.S., primarily via a paper by two long-time proponents of embryonic stem cells (though this is not disclosed in the article or in the paper), but paints a broad-brush across clinics operating legally and ethically as well as the shady operators. It then juxtaposes the critique of U.S. stem cell clinics with the tragic story of a patient who traveled to three different overseas clinics to receive stem cell injections and developed a growing mass of cells on his spine from at least one of the injections.

The implied warning is that all U.S. adult stem cell clinics are using similar methods, and, by extension, their patients may experience similar problems. Indeed, many clinics are offshore to avoid FDA rules, but yet again the article drops adjectives and sows confusion. The New England Journal of Medicine source on the case notes that the patient supposedly received proliferating cells including embryonic and fetal stem cells.

Certainly all clinics should operate within appropriate ethical and legal boundaries and patients should receive all information, including published background and whether the cells being used are adult, fetal, or embryonic; this is simply a matter of getting full informed consent. But fearmongering and misinformation help neither the patients nor the science.

The stem cell science deniers continue to denigrate adult stem cells, denying their successes or even at times their existence by dropping the necessary, descriptive adjective. But for patients, adult stem cells are the true gold standard for stem cells. The hope of adult stem cells is being realized right now, for thousands of people around the globe. Those stories, those doctors, those patients who have been helped by adult stem cell treatments, deserve to be heard. People like Cindy Schroeder who thought she was given a death sentence when she was diagnosed with multiple myeloma.

But Cindys doctor was informed on the facts of modern medicine, and was able to inform Cindy and her family that there was hopefrom adult stem cells. Over a year after her stem cell treatment, Cindy leads a full, active life and her family is closer than ever. Her story, like that of thousands of others, is not theoretical; its real adult stem cell science.

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Hundreds of U.S. clinics are selling unapproved stem cell …

By Stem Cell Clinics

Hundreds of clinics across the United States are marketing unapproved stem cell treatments for conditions ranging from aging skin to spinal cord injuries, a new study finds.

In an online search, researchers found at least 570 clinics offering unapproved stem cell "therapies." They tend to be concentrated in a handful of states -- including Arizona, California, Colorado, Florida, New York and Texas -- but are scattered across many other states, too.

Most often, the clinics market stem cell procedures for orthopedic conditions, such as arthritis and injured ligaments and tendons. This does have science behind it, but is still experimental, medical experts said.

In other cases with little or no supporting evidence, clinics hawked stem cell "facelifts" and therapies for serious conditions such as chronic lung disease, Parkinson's disease and multiple sclerosis.

If these pricey stem cell treatments are unproven and unapproved by federal regulators, how can these clinics exist?

"I ask myself that question all the time," said Leigh Turner, a bioethicist who worked on the study.

Turner, an associate professor at the University of Minnesota's Center for Bioethics, said attention used to focus on "stem cell tourism" -- where people travel to countries such as China, India and Mexico to get unproven treatments.

"I think there's a misperception that everything here [in the U.S.] is regulated," Turner said. "But these clinics are operating here, and on a relatively large scale."

Stem cells are primitive cells with the potential to mature into various types of body tissue. Medical researchers have been studying the possibility of using stem cells to repair damaged tissue in a range of chronic ills -- with limited success so far.

But the general public has heard about the "promise" of stem cells for years, and it can be easy to be taken in by clinics' marketing tactics, Turner said.

Websites can, for instance, link to published medical studies that make their therapies seem legitimate, Turner said. "These businesses can be quite savvy," he said. "I think it's asking too much to just tell consumers to be wary. We need to be asking, why should these clinics be allowed to do this?"

Arthur Caplan, a bioethicist who was not involved in the study, cited some explanations for the growth of stem cell clinics.

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The businesses are usually not engaging in interstate commerce, which helps them "fly under the radar," said Caplan, who directs the division of medical ethics at NYU Langone Medical Center in New York City.

Plus, he said, there's a regulatory gray area when it comes to so-called "autologous" stem cell therapy -- which refers to treatments that use a person's own stem cells.

"If you have cells from your own body reinjected, it isn't clear that you're getting a 'new biologic,' " Caplan explained.

Of the businesses Turner's team found, most marketed autologous therapies, usually using stem cells from people's body fat or bone marrow. But about one-fifth of the businesses claimed to use stem cells from umbilical cord blood or amniotic or placental tissue.

The issue goes beyond people wasting their money or having their "hopes dashed," Turner said. It's known some have been seriously harmed.

He mentioned two elderly patients in Florida who died following an unapproved stem cell procedure.

The U.S. Food and Drug Administration has taken steps against specific businesses. Last year, it sent a warning letter to a network of clinics that operate in California, Florida and New York. According to the FDA, the clinics illegally use stem cells from people's fat tissue to treat conditions such as Parkinson's, MS, amyotrophic lateral sclerosis (ALS) and autism.

"Many of these claims are outrageous," Caplan said. "These clinics are preying on vulnerable people."

His advice for consumers: "Be wary of any procedure that comes with celebrity endorsements or patient testimonials."

The FDA has issued draft guidelines on the use of stem cells. A public hearing is scheduled for later this year.

The new study findings appear in the June 30 issue of Cell Stem Cell.

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Hundreds of U.S. clinics are selling unapproved stem cell ...

Purest yet liver-like cells generated from induced …

By Induced Pluripotent Stem Cells

This image shows induced pluripotent stem cells expressing a characteristic cell surface protein called SSEA4 (green). A research team including developmental biologist Stephen A. Duncan, D. Phil., SmartStateTM Chair of Regenerative Medicine at the Medical University of South Carolina (MUSC), has found a better way to purify liver cells made from induced pluripotent stem cells (iPSCs). Their efforts, published August 25, 2016 in Stem Cell Reports, will aid studies of liver disease for the National Heart, Lung, and Blood Institute (NHLBI)'s $80 million Next Generation Genetic Association Studies (Next Gen) Program. The University of Minnesota (Minneapolis) and the Medical College of Wisconsin (Milwaukee) contributed to the study.

This new methodology could facilitate progress toward an important clinical goal: the treatment of patients with disease-causing mutations in their livers by transplant of unmutated liver cells derived from their own stem cells. Previous attempts to generate liver-like cells from stem cells have yielded heterogeneous cell populations that bear little resemblance to diseased livers in patients.

NHLBI's Next Gen was created to bank stem cell lines sourced from patients in genome-wide association studies (GWAS). The goal of the NHLBI Next Gen Lipid Conditions sub-section--a collaborative effort between Duncan and Daniel J. Rader, M.D., and Edward E. Morrisey, Ph.D., both at the University of Pennsylvania--is to help determine the genetic sources of heart, lung, or blood conditions that also encompass the liver. These GWAS studies map the genomes in hundreds of people as a way to look for genetic mutation patterns that differ from the genomes of healthy individuals.

A GWAS study becomes more powerful--more likely to find the correct genetic mutations that cause a disease--as more genomes are mapped. Once a panel of suspected mutations is built, stem cells from these individuals can be "pushed" in culture dishes to differentiate into any of the body's cells, as for example liver-, heart-, or vascular-like cells. The cells can be screened in high-throughput formats (i.e., cells are expanded and cultured in many dishes) to learn more about the mutations and to test panels of drugs that might ultimately help treat patients harboring a disease.

The problem arises during the "pushing." For example, iPSCs stubbornly refuse to mature uniformly into liver-like cells when fed growth factors. Traditionally, antibodies have been used to recognize features of maturity on the surfaces of cells and purify cells that are alike. This approach has been crucial to stem cell research, but available antibodies that recognize mature liver cells are few and tend to recognize many different kinds of cells. The many types of cells in mixed populations have diverse characteristics that can obscure underlying disease-causing genetic variations, which tend to be subtle.

"Without having a pure population of liver cells, it was incredibly difficult to pick up these relatively subtle differences caused by the mutations, but differences that are important in the life of an individual," said Duncan.

Instead of relying on antibodies, Duncan and his crew embraced a new technology called chemoproteomic cell surface capture (CSC) technology. True to its name, CSC technology allowed the group to map the proteins on the surface of liver cells that were most highly produced during the final stages of differentiation of stem cells into liver cells. The most abundant protein was targeted with an antibody labeled with a fluorescent marker and used to sort the mature liver cells from the rest.

The procedure was highly successful: the team had a population of highly pure, homogeneous, and mature liver-like cells. Labeled cells had far more similar traits of mature hepatocytes than unlabeled cells. Pluripotent stem cells that had not differentiated were excluded from the group of labeled cells.

"That's important," said Duncan. "If you're wanting to transplant cells into somebody that has liver disease, you really don't want to be transplanting pluripotent cells because pluripotent cells form tumors called teratocarcinomas."

Duncan cautions that transplantation of iPSC-derived liver cells is not yet ready for translation to the clinic. But the technology for sorting homogeneous liver cells can be used now to successfully and accurately model and study disease in the cell culture dish.

"We think that by being able to generate pure populations, it will get rid of the variability, and therefore really help us combine with GWAS studies to identify allelic variations that are causative of a disease, at least in the liver," said Duncan.

Source: Medical University of South Carolina

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What are human embryonic stem cells used for? | Europe’s stem …

By Embryonic Stem Cells

Human embryonic stem cells (hESCs) can be used in research to:

Researchers can use hESCs to produce specialized cells like nerve or heart cells in the lab. These specialized cells can be studied in detail to understand more about the causes and development of diseases. They can also be used to reveal how our cells react to, or could be treated with potential new drugs. This is particularly useful for studying types of cells that cannot easily be obtained by taking tissue from patients, e.g. brain cells.

Recently, hESCs have been produced that meet the strict quality requirements for use in medical treatments. These clinical grade hESCs have been approved for use in a small number of early clinical trials. One example is a trial led by The London Project to Cure Blindness, using hESCs to produce a particular type of eye cell for treatment of patients with the eye disease age-related macular degeneration. The biotechnology company ACT is also using human ESCs to make cells for patients with an eye disease: Stargardts macular dystrophy.

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Regenerative Medicine Conferences | Tissue Engineering …

By Uncategorized

The 5th International Conference on Tissue Engineering & Regenerative Medicine which is going to be held during September 12-14, 2016 at Berlin, Germany will bring together world-class personalities working on stem cells, tissue engineering and regenerative medicine to discuss materials-related strategies for disease remediation and tissue repair.

Tissue Regeneration

In the field of biology, regeneration is the progression of renewal, regeneration and growth that makes it possible for genomes, cells, organ regeneration to natural changes or events that cause damage or disturbance.This study is carried out as craniofacial tissue engineering, in-situtissue regeneration, adipose-derived stem cells for regenerative medicine which is also a breakthrough in cell culture technology. The study is not stopped with the regeneration of tissue where it is further carried out in relation with cell signaling, morphogenetic proteins. Most of the neurological disorders occurred accidental having a scope of recovery by replacement or repair of intervertebral discs repair, spinal fusion and many more advancements. The global market for tissue engineering and regeneration products such as scaffolds, tissueimplants, biomimetic materials reached $55.9 billion in 2010 and it is expected to reach $89.7 billion by 2016 at a compounded annual growth rate (CAGR) of 8.4%. It grows to $135 billion by 2024.

Related Conferences

5th InternationalConference on Tissue Engineering and Regenerative Medicine September 12-14, 2016 Berlin, Germany; 5th International Conference onCell and Gene Therapy May 19-21, 2016 San Antonio, USA; InternationalConference on Cancer Immunologyand ImmunotherapyJuly 28-30, 2016 Melbourne, Australia; InternationalConference on Molecular BiologyOctober 13-15, 2016 Dubai, UAE; Tissue Niches and Resident Stem Cells in Adult Epithelia Gordon Research Conference, Regulation of Tissue Homeostasis by Signalling in the Stem Cell Niche August 7-12, Hong Kong, China; 10 Years of IPSCs, Cell Symposia, September 25-27, 2016 Berkeley, CA, USA; World Stem Cells and Regenerative Medicine Congress May 18-20, 2016 London, UK; Notch Signaling in Development, Regeneration and Disease Gordon Research Conference, July 31-August 5, 2016 Lewiston, ME, USA

Designs for Tissue Engineering

The developing field of tissue engineering aims to regenerate damaged tissues by combining cells from the body withbioresorbablematerials, biodegradable hydrogel, biomimetic materials, nanostructures andnanomaterials, biomaterials and tissue implants which act as templates for tissue regeneration, to guide the growth of new tissue by using with the technologies. The global market for biomaterials, nanostructures and bioresorbable materials are estimated to reach $88.4 billion by 2017 from $44.0 billion in 2012 growing at a CAGR of 15%. Further the biomaterials market estimated to be worth more than 300 billion US Dollars and to be increasing 20% per year.

Related Conferences

5th International ConferenceonCell and Gene Therapy May 19-21, 2016 San Antonio, USA; International Conference on Restorative Medicine October 24-26, 2016 Chicago, USA; InternationalConference on Molecular Biology October 13-15, 2016 Dubai, UAE; 2nd International Conference on Bio-banking August 18-19, 2016 Portland, USA; ISSCR Annual Meeting 22-25 June, 2016 San Francisco, California, USA; Keystone Cardiac Development, Regeneration and Repair (Z2) April 3 7, 2016 Snowbird, Utah, USA;EMBL Hematopoietic Stem Cells: From the Embryo to the Aging Organism, June 3-5, 2016 Heidelberg, Germany; ISSCR Pluripotency: From basic science to therapeutic applications March 22-24, 2016 Kyoto, Japan

Organ Engineering

This interdisciplinary engineering has attracted much attention as a new therapeutic means that may overcome the drawbacks involved in the current artificial organs and organtransplantationthat have been also aiming at replacing lost or severely damaged tissues or organs. Tissue engineering and regenerative medicine is an exciting research area that aims at regenerative alternatives to harvested tissues for organ transplantation with soft tissues. Although significant progress has been made in thetissue engineeringfield, many challenges remain and further development in this area will require ongoing interactions and collaborations among the scientists from multiple disciplines, and in partnership with the regulatory and the funding agencies. As a result of the medical and market potential, there is significant academic and corporate interest in this technology.

Related Conferences

International Conference on Restorative Medicine October 24-26, 2016 Chicago, USA; 5th InternationalConference on Cell and Gene Therapy May 19-21, 2016 San Antonio, USA; 5th International Conference on Regenerative Medicine September 12-14, 2016 Berlin, Germany; 2nd International Conference on Tissue preservation August 18-19, 2016 Portland, USA;Cell and Gene TherapyJanuary 25-27, 2016 Washington D.C., USA; ISSCR Stem Cell Models of Neural Degeneration and Disease February 1-3, 2016 Dresden, Germany; Craniofacial Morphogenesis and Tissue Regeneration March 12-18, 2016 California, USA; Keystone Stem Cells and Cancer (C1) March 6-10, Colorado, USA; Keystone Stem Cells and Regeneration in the Digestive Organs (X6) March 13 17 Colorado, USA

Cancer Stem Cells

The characterization of cancer stem cell is done by identifying the cell within a tumor that possesses the capacity to self-renew and to cause theheterogeneous lineagesof cancer cells that comprise the tumor. This stem cell which acts as precursor for the cancer acts as a tool against it indulging the reconstruction of cancer stem cells, implies as the therapeutic implications and challenging the gaps globally. The global stem cell market will grow from about $5.6 billion in 2013 to nearly $10.6 billion in 2018, registering a compound annual growth rate (CAGR) of 3.6% from 2013 through 2018. The Americas is the largest region of globalstem cellmarket, with a market share of about $2.0 billion in 2013. The region is projected to increase to nearly $3.9 billion by 2018, with a CAGR of 13.9% for the period of 2013 to 2018. Europe is the second largest segment of the global stem cell market and is expected to grow at a CAGR of 13.4% reaching about $2.4 billion by 2018 from nearly $1.4 billion in 2013.

Related Conferences

5th InternationalConference Cell and Gene Therapy May 19-21, 2016 San Antonio, USA; International Conference on Molecular Biology October 13-15, 2016 Dubai, UAE; 5th International Conference on Tissue EngineeringSeptember 12-14, 2016 Berlin, Germany; 2nd International Conference on Tissue preservationAugust 18-19, 2016 Portland, USA; Molecular and Cellular Basis of Growth and Regeneration (A3) January 10 14, 2016 Colorado, USA; Cell and Gene TherapyJanuary 25-27, 2016 Washington D.C., USA; ISSCR Stem Cell Models of Neural Degeneration and Disease March 13 17, 2016 Dresden, Germany; Craniofacial Morphogenesis and Tissue Regeneration March 12-18, 2016 California, USA; World Stem Cells Congress May 18-20, 2016 London, UK

Bone Tissue Engineering

Tissue engineering ofmusculoskeletal tissues, particularly bone and cartilage, is a rapidly advancing field. In bone, technology has centered on bone graft substitute materials and the development of biodegradable scaffolds. Recently, tissue engineering strategies have included cell and gene therapy. The availability of growth factors and the expanding knowledge base concerning the bone regeneration with modern techniques like recombinant signaling molecules, solid free form fabrication of scaffolds, synthetic cartilage, Electrochemical deposition,spinal fusionand ossification are new generated techniques for tissue-engineering applications. The worldwide market for bone and cartilage repairs strategies is estimated about $300 million. During the last 10/15 years, the scientific community witnessed and reported the appearance of several sources of stem cells with both osteo and chondrogenic potential.

Related Conferences

5th International Conference on Tissue Engineering and Regenerative Medicine September 12-14, 2016 Berlin, Germany; 3rd 2nd International Conference on Tissue preservation and Bio-banking August 18-19, 2016 Portland, USA; 5th International Conference on Cell and Gene Therapy May 19-21, 2016 San Antonio, USA; International Conference on Restorative Medicine October 24-26, 2016 Chicago, USA; 10th World Biomaterials Congress May 17-22, 2016 Quebec, Canada; 2016 TERMIS-EU Conference June 28- July1, 2016 Uppsala, Sweden; 2016 TERMIS-AP Conference Tamsui Town of New Taipei City May 23-28, 2016; 2016 TERMIS-AM Conference September 3-6, 2016, San Diego, USA; Pluripotency: From basic science to therapeutic applications 22-24 March 2016 Kyoto, Japan

Scaffolds

Scaffolds are one of the three most important elements constituting the basic concept of regenerative medicine, and are included in the core technology of regenerative medicine. Every day thousands of surgical procedures are performed to replace or repair tissue that has been damaged through disease or trauma. The developing field of tissue engineering (TE) aims to regeneratedamaged tissuesby combining cells from the body with highly porous scaffold biomaterials, which act as templates for tissue regeneration, to guide the growth of new tissue. Scaffolds has a prominent role in tissue regeneration the designs, fabrication, 3D models, surface ligands and molecular architecture, nanoparticle-cell interactions and porous of thescaffoldsare been used in the field in attempts to regenerate different tissues and organs in the body. The world stem cell market was approximately 2.715 billion dollars in 2010, and with a growth rate of 16.8% annually, a market of 6.877 billion dollars will be formed in 2016. From 2017, the expected annual growth rate is 10.6%, which would expand the market to 11.38 billion dollars by 2021.

Related Conferences

InternationalConference on Restorative MedicineOctober 24-26, 2016 Chicago, USA; 5th InternationalConference onCell and Gene TherapyMay 19-21, 2016 San Antonio, USA; 5th InternationalConference on Regenerative MedicineSeptember 12-14, 2016 Berlin, Germany; 2ndInternational Conference on Tissue preservationAugust 18-19, 2016 Portland, USA;Cell and Gene TherapyJanuary 25-27, 2016 Washington D.C., USA; ISSCRStem Cell Modelsof Neural Degeneration and Disease February 1-3, 2016 Dresden, Germany; Craniofacial Morphogenesis andTissue RegenerationMarch 12-18, 2016 California, USA; KeystoneStem Cells and Cancer(C1) March 6-10, Colorado, USA; KeystoneStem Cells and Regenerationin the Digestive Organs (X6) March 13 17 Colorado, USA

Tissue Regeneration Technologies

Guided tissue regeneration is defined as procedures attempting to regenerate lost periodontal structures through differential tissue responses. Guidedbone regenerationtypically refers to ridge augmentation or bone regenerative procedures it typically refers to regeneration of periodontal therapy. The recent advancements and innovations in biomedical and regenerative tissue engineering techniques include the novel approach of guided tissue regeneration and combination ofnanotechnologyand regenerative medicine.

Related Conferences

5th InternationalConferenceCell and Gene TherapyMay 19-21, 2016 San Antonio, USA; InternationalConference on Restorative MedicineOctober 24-26, 2016 Chicago, USA; InternationalConference on Molecular BiologyOctober 13-15, 2016 Dubai, UAE; 2nd InternationalConference on Bio-bankingAugust 18-19, 2016 Portland, USA;ISSCR Annual Meeting22-25 June, 2016 San Francisco, California, USA; KeystoneCardiac Development, Regeneration and Repair (Z2) April 3 7, 2016 Snowbird, Utah, USA;EMBLHematopoietic Stem Cells: From the Embryo to the Aging Organism, June 3-5, 2016 Heidelberg, Germany; ISSCRPluripotency: From basic science to therapeutic applications March 22-24, 2016 Kyoto, Japan

Regeneration and Therapeutics

Regenerative medicinecan be defined as a therapeutic intervention which replaces or regenerates human cells, tissues or organs, to restore or establish normal function and deploys small molecule drugs, biologics, medical devices and cell-based therapies. It deals with the different therapeutic uses like stem cells for tissue repair, tissue injury and healing process, cardiacstem cell therapyfor regeneration, functional regenerative recovery, effects of aging on tissuerepair/regeneration, corneal regeneration & degeneration. The global market is expected to reach $25.5 billion by 2011 and will further grow to $36.1 billion by 2016 at a CAGR of 7.2%. It is expected to reach $65 billion mark by 2024.

Related Conferences

5th InternationalConference on Tissue Engineering and Regenerative MedicineSeptember 12-14, 2016 Berlin, Germany; 5th InternationalConference onCell and Gene TherapyMay 19-21, 2016 San Antonio, USA; InternationalConference on Cancer Immunologyand ImmunotherapyJuly 28-30, 2016 Melbourne, Australia; InternationalConference on Molecular BiologyOctober 13-15, 2016 Dubai, UAE; Tissue Niches andResident Stem Cells in Adult EpitheliaGordon Research Conference,Regulation of Tissue Homeostasisby Signalling in the Stem Cell Niche August 7-12, Hong Kong, China;10 Years of IPSCs, Cell Symposia, September 25-27, 2016 Berkeley, CA, USA; WorldStem Cells and Regenerative Medicine CongressMay 18-20, 2016 London, UK; Notch Signaling in Development,Regenerationand Disease Gordon Research Conference, July 31-August 5, 2016 Lewiston, ME, USA

Regenerative medicine

Regenerative medicine is a branch oftranslational researchin tissue engineering and molecular biology which deals with the process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function. The latest developments involve advances in cell and gene therapy and stem cell research, molecular therapy, dental and craniofacial regeneration.Regenerative medicineshave the unique ability to repair, replace and regenerate tissues and organs, affected due to some injury, disease or due to natural aging process. These medicines are capable of restoring the functionality of cells and tissues. The global regenerative medicine market will reach $ 67.6 billion by 2020 from $16.4 billion in 2013, registering a CAGR of 23.2% during forecast period (2014 - 2020). Small molecules and biologics segment holds prominent market share in the overall regenerative medicine technology market and is anticipated to grow at a CAGR of 18.9% during the forecast period.

Related Conferences

InternationalConference on Restorative MedicineOctober 24-26, 2016 Chicago, USA; 5th InternationalConference onCell and Gene TherapyMay 19-21, 2016 San Antonio, USA; 5th InternationalConference on Regenerative MedicineSeptember 12-14, 2016 Berlin, Germany; 2ndInternational Conference on Tissue preservationAugust 18-19, 2016 Portland, USA;Cell and Gene TherapyJanuary 25-27, 2016 Washington D.C., USA; ISSCRStem Cell Modelsof Neural Degeneration and Disease February 1-3, 2016 Dresden, Germany; Craniofacial Morphogenesis andTissue RegenerationMarch 12-18, 2016 California, USA; KeystoneStem Cells and Cancer(C1) March 6-10, Colorado, USA; KeystoneStem Cells and Regenerationin the Digestive Organs (X6) March 13 17 Colorado, USA

Applications of Tissue Engineering

The applications of tissue engineering and regenerative medicine are innumerable as they mark the replacement of medication andorgan replacement. The applications involve cell tracking andtissue imaging, cell therapy and regenerative medicine, organ harvesting, transport and transplant, the application of nanotechnology in tissue engineering and regenerative medicine and bio banking. Globally the research statistics are increasing at a vast scale and many universities and companies are conducting events on the subject regenerative medicine conference like tissue implants workshops, endodontics meetings, tissue biomarkers events, tissue repair meetings, regenerative medicine conferences, tissue engineering conference, regenerative medicine workshop, veterinary regenerative medicine, regenerative medicine symposiums, tissue regeneration conferences, regenerative medicine congress.

Related Conferences

5th InternationalConferenceCell and Gene TherapyMay 19-21, 2016 San Antonio, USA; InternationalConference on Restorative MedicineOctober 24-26, 2016 Chicago, USA; InternationalConference on Molecular BiologyOctober 13-15, 2016 Dubai, UAE; 2nd InternationalConference on Bio-bankingAugust 18-19, 2016 Portland, USA;ISSCR Annual Meeting22-25 June, 2016 San Francisco, California, USA; KeystoneCardiac Development, Regeneration and Repair (Z2) April 3 7, 2016 Snowbird, Utah, USA;EMBLHematopoietic Stem Cells: From the Embryo to the Aging Organism, June 3-5, 2016 Heidelberg, Germany; ISSCRPluripotency: From basic science to therapeutic applications March 22-24, 2016 Kyoto, Japan

Regenerative Medicine Market

There are strong pricing pressures from public healthcare payers globally as Governments try to reduce budget deficits. Regenerative medicine could potentially save public health bodies money by reducing the need for long-term care and reducing associated disorders, with potential benefits for the world economy as a whole.The global market fortissue engineeringand regeneration products reached $55.9 billion in 2010, is expected to reach $59.8 billion by 2011, and will further grow to $89.7 billion by 2016 at a compounded annual growth rate (CAGR) of 8.4%. It grows to $135 billion to 2024. The contribution of the European region was 43.3% of the market in 2010, a value of $24.2 billion. Themarketis expected to reach $25.5 billion by 2011 and will further grow to $36.1 billion by 2016 at a CAGR of 7.2%. It grows to $65 billion to 2024.

Related Conferences

5th InternationalConference on Tissue Engineeringand Regenerative MedicineSeptember 12-14, 2016 Berlin, Germany; 3rd 2nd InternationalConference on Tissue preservationand Bio-bankingAugust 18-19, 2016 Portland, USA; 5th InternationalConference on Cell and Gene TherapyMay 19-21, 2016 San Antonio, USA; InternationalConference on Restorative MedicineOctober 24-26, 2016 Chicago, USA; 10thWorld Biomaterials CongressMay 17-22, 2016 Quebec, Canada; 2016TERMIS-EU ConferenceJune 28- July1, 2016 Uppsala, Sweden; 2016TERMIS-AP ConferenceTamsui Town of New Taipei City May 23-28, 2016; 2016TERMIS-AM ConferenceSeptember 3-6, 2016, San Diego, USA;Pluripotency: From basic science to therapeutic applications22-24 March 2016 Kyoto, Japan

Regenerative Medicine Europe

Leading EU nations with strong biotech sectors such as the UK and Germany are investing heavily in regenerative medicine, seeking competitive advantage in this emerging sector. The commercial regenerative medicine sector faces governance challenges that include a lack of proven business models, an immature science base and ethical controversy surrounding hESC research. The recent global downturn has exacerbated these difficulties: private finance has all but disappeared; leading companies are close to bankruptcy, and start-ups are struggling to raise funds. In the UK the government has responded by announcing 21.5M funding for the regenerative medicine industry and partners. But the present crisis extends considerably beyond regenerative medicine alone, affecting much of the European biotech sector. A 2009 European Commission (EC) report showed the extent to which the global recession has impacted on access to VC finance in Europe: 75% of biopharma companies in Europe need capital within the next two years if they are to continue their current range of activities.

Related Conferences

InternationalConference on Restorative MedicineOctober 24-26, 2016 Chicago, USA; 5th InternationalConference onCell and Gene TherapyMay 19-21, 2016 San Antonio, USA; 5th InternationalConference on Regenerative MedicineSeptember 12-14, 2016 Berlin, Germany; 2ndInternational Conference on Tissue preservationAugust 18-19, 2016 Portland, USA;Cell and Gene TherapyJanuary 25-27, 2016 Washington D.C., USA; ISSCRStem Cell Modelsof Neural Degeneration and Disease February 1-3, 2016 Dresden, Germany; Craniofacial Morphogenesis andTissue RegenerationMarch 12-18, 2016 California, USA; KeystoneStem Cells and Cancer(C1) March 6-10, Colorado, USA; KeystoneStem Cells and Regenerationin the Digestive Organs (X6) March 13 17 Colorado, USA

Embryonic Stem Cell

Embryonic stem cells are pluripotent, meaning they are able to grow (i.e. differentiate) into all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body as long as they are specified to do so. Embryonic stem cells are distinguished by two distinctive properties: their pluripotency, and their ability to replicate indefinitely. ES cells are pluripotent, that is, they are able to differentiate into all derivatives of the three primary germ layers: ectoderm, endoderm, and mesoderm. These include each of the more than 220 cell types in the adult body. Pluripotency distinguishes embryonic stem cells from adult stem cells found in adults; while embryonic stem cells can generate all cell types in the body, adult stem cells are multipotent and can produce only a limited number of cell types. Additionally, under defined conditions, embryonic stem cells are capable of propagating themselves indefinitely. This allows embryonic stem cells to be employed as useful tools for both research and regenerative medicine, because they can produce limitless numbers of themselves for continued research or clinical use.

Related Conferences

5th InternationalConference on Tissue Engineering and Regenerative MedicineSeptember 12-14, 2016 Berlin, Germany; 5th InternationalConference onCell and Gene TherapyMay 19-21, 2016 San Antonio, USA; InternationalConference on Cancer Immunologyand ImmunotherapyJuly 28-30, 2016 Melbourne, Australia; InternationalConference on Molecular BiologyOctober 13-15, 2016 Dubai, UAE; Tissue Niches andResident Stem Cells in Adult EpitheliaGordon Research Conference,Regulation of Tissue Homeostasisby Signalling in the Stem Cell Niche August 7-12, Hong Kong, China;10 Years of IPSCs, Cell Symposia, September 25-27, 2016 Berkeley, CA, USA; WorldStem Cells and Regenerative Medicine CongressMay 18-20, 2016 London, UK; Notch Signaling in Development,Regenerationand Disease Gordon Research Conference, July 31-August 5, 2016 Lewiston, ME, USA

Stem Cell Transplant

Stem cell transplantation is a procedure that is most often recommended as a treatment option for people with leukemia, multiple myeloma, and some types of lymphoma. It may also be used to treat some genetic diseases that involve the blood. During a stem cell transplant diseased bone marrow (the spongy, fatty tissue found inside larger bones) is destroyed with chemotherapy and/or radiation therapy and then replaced with highly specialized stem cells that develop into healthy bone marrow. Although this procedure used to be referred to as a bone marrow transplant, today it is more commonly called a stem cell transplant because it is stem cells in the blood that are typically being transplanted, not the actual bone marrow tissue.

Related Conferences

5th InternationalConference Cell and Gene TherapyMay 19-21, 2016 San Antonio, USA; InternationalConference on Molecular BiologyOctober 13-15, 2016 Dubai, UAE; 5th InternationalConference on Tissue EngineeringSeptember 12-14, 2016 Berlin, Germany; 2nd InternationalConference on Tissue preservationAugust 18-19, 2016 Portland, USA; Molecular and Cellular Basis ofGrowth and Regeneration(A3) January 10 14, 2016 Colorado, USA;Cell and Gene TherapyJanuary 25-27, 2016 Washington D.C., USA; ISSCRStem Cell Modelsof Neural Degeneration and Disease March 13 17, 2016 Dresden, Germany; Craniofacial Morphogenesis andTissue RegenerationMarch 12-18, 2016 California, USA;World Stem Cells CongressMay 18-20, 2016 London, UK

Market Analysis Report:

Tissue engineering is an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ. Regenerative medicine is not one discipline. It can be defined as a therapeutic intervention which replaces or regenerates human cells, tissues or organs, to restore or establish normal function and deploys small molecule drugs, biologics, medical devices and cell-based therapies

Currently it has emerged as a rapidly diversifying field with the potential to address the worldwide organ shortage issue and comprises of tissue regeneration and organ replacement. Regenerative medicine could potentially save public health bodies money by reducing the need for long-term care and reducing associated disorders, with potential benefits for the world economy as a whole.The global tissue engineering and regeneration market reached $17 billion in 2013. This market is expected to grow to nearly $20.8 billion in 2014 and $56.9 billion in 2019, a compound annual growth rate (CAGR) of 22.3%. On the basis of geography, Europe holds the second place in the global market in the field of regenerative medicine & tissue engineering. In Europe countries like UK, France and Germany are possessing good market shares in the field of regenerative medicine and tissue engineering. Spain and Italy are the emerging market trends for tissue engineering in Europe.

Tissue engineering is "an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ. Currently it has emerged as a rapidly diversifying field with the potential to address the worldwide organ shortage issue and comprises of tissue regeneration and organ replacement. A novel set of tissue replacement parts and implementation strategies had shown a great revolution in this field. Cells placed on or within the tissue constructs is the most common methodology in tissue engineering.

Regenerative medicine is not one discipline. It can be defined as a therapeutic intervention which replaces or regenerates human cells, tissues or organs, to restore or establish normal function and deploys small molecule drugs, biologics, medical devices and cell-based therapies

This field continues to evolve. In addition to medical applications, non-therapeutic applications include using tissues as biosensors to detect biological or chemical threat agents, and tissue chips that can be used to test the toxicity of an experimental medication. Tissue Engineering and Regenerative Medicine is the major field in Medicine, which is still under research and the advancements are maximizing day to day.

Regenerative Medicine-2015 is an engrossed a vicinity of cognizant discussions on novel subjects like Tissue Regeneration, Materials & Designs for Tissue Engineering, Stem CellTools to Battle Cancer, Bioreactors in Tissue Engineering, Regeneration & Therapeutics, Cord Blood & Regenerative Medicine and Clinical Medicine, to mention a few. The three days event implants a firm relation of upcoming strategies in the field of Tissue Science & Regenerative Medicine with the scientific community. The conceptual and applicable knowledge shared, will also foster organizational collaborations to nurture scientific accelerations.We bring together business, creative, and technology leaders from the tissue engineering, marketing, and research industry for the most current and relevant.

Berlin is one of the largest and most diverse science regions in Europe. Roughly 200,000 people from around the world teach, research, work and study here. Approximately 17 percent of all students come from abroad, most of them from China, Russia and the USA. Many cooperative programs link Berlins institutes of higher education with partner institutes around the world. Berlin is a city of science at the heart of Europe a city whose history of scientific excellence stems from its many important research institutions and its long track record of scientific breakthroughs. Berlin has numerous modern Technology Centers. Their science-oriented infrastructure makes them attractive locations for young, technology-oriented companies.

Germany places great emphasis on globally networked research cooperation. Many organizations support international researchers and academics: Today more than 32,000 are being supported with scholarships. Besides this, research funding in Germany has the goal of financing the development of new ideas and technologies. The range covers everything from basic research in natural sciences, new technologies to structural research funding at institutions of higher education. On the basis of geography, the regenerative medicine bone and joint market Europe hold the second place in the global market in the field of regenerative medicine & tissue engineering. The market growth is expected to reach $65 billion by 2024 in Europe. In Europe countries like UK, France, and Germany are possessing good market share in the field of regenerative medicine and tissue engineering. Spain and Italy are the emerging market trends for tissue engineering in Europe. As per the scope and emerging market for tissue engineering and regenerative medicine Berlin has been selected as Venue for the 5th International Conference on Tissue Science and Regenerative Medicine.

Meet Your Target MarketWith members from around the world focused on learning about Advertising and marketing, this is the single best opportunity to reach the largest assemblage of participants from the tissue engineering and regenerative medicine community. The meeting engrossed a vicinity of cognizant discussions on novel subjects like Tissue Regeneration, Materials & Designs for Tissue Engineering, Stem CellTools to Battle Cancer, Bioreactors in Tissue Engineering, Regeneration & Therapeutics, Cord Blood & Regenerative Medicine and Clinical Medicine, to mention a few. The three days event implants a firm relation of upcoming strategies in the field of Tissue Engineering & Regenerative Medicine with the scientific community. The conceptual and applicable knowledge shared, will also foster organizational collaborations to nurture scientific accelerations.Conduct demonstrations, distribute information, meet with current and potential customers, make a splash with a new product line, and receive name recognition.

International Stem Cell Forum (ISCF)

International Society for Stem Cell Research (ISSCR)

UK Medical Research Council (MRC)

Australian Stem Cell Center

Canadian Institutes of Health Research (CIHR)

Euro Stem Cell (ACR)

Center for Stem Cell Biology

Stem Cell Research Singapore

UK National Stem Cell Network

Spain Mobile Marketing Association

European Marketing Confederation (EMC)

European Letterbox Marketing Association(ELMA)

European Sales & Marketing Association (ESMA)

The Incentive Marketing Association (IMA Europe)

European Marketing Academy

Figure 1: Statistical Analysis of Societies and Associations

Source: Reference7

Presidents or Vice Presidents/ Directors of Associations and Societies, CEOs of the companies associated with regenerative medicine and tissue engineering Consumer Products. Retailers, Marketing, Advertising and Promotion Agency Executives, Solution Providers (digital and mobile technology, P-O-P design, retail design, and retail execution), Professors and Students from Academia in the study of Marketing and Advertising filed.

Industry 40%

Academia 50%

Others 10%

See original here:
Regenerative Medicine Conferences | Tissue Engineering ...

Stem Cell Conferences | Cell and Stem Cell Congress | Stem …

By Stem Cell Treatment

On behalf of the organizing committee, it is my distinct pleasure to invite you to attend the Stem Cell Congress-2017. After the success of the Cell Science-2011, 2012, 2013, 2014, 2015, Conference series.LLC is proud to announce the 6th World Congress and expo on Cell & Stem Cell Research (Stem Cell Congress-2017) which is going to be held during March 20-22, 2017, Orlando, Florida, USA. The theme of Stem Cell Congress-2017 is Explore and Exploit the Novel Techniques in Cell and Stem Cell Research.

This annual Cell Science conference brings together domain experts, researchers, clinicians, industry representatives, postdoctoral fellows and students from around the world, providing them with the opportunity to report, share, and discuss scientific questions, achievements, and challenges in the field.

Examples of the diverse cell science and stem cell topics that will be covered in this comprehensive conference include Cell differentiation and development, Cell metabolism, Tissue engineering and regenerative medicine, Stem cell therapy, Cell and gene therapy, Novel stem cell technologies, Stem cell and cancer biology, Stem cell treatment, Tendency in cell biology of aging and Apoptosis and cancer disease, Drugs and clinical developments. The meeting will focus on basic cell mechanism studies, clinical research advances, and recent breakthroughs in cell and stem cell research. With the support of many emerging technologies, dramatic progress has been made in these areas. In Stem Cell Congress-2017, you will be able to share experiences and research results, discuss challenges encountered and solutions adopted and have opportunities to establish productive new academic and industry research collaborations.

In association with the Stem Cell Congress-2017 conference, we will invite those selected to present at the meeting to publish a manuscript from their talk in the journal Cell Science with a significantly discounted publication charge. Please join us in Philadelphia for an exciting all-encompassing annual Stem Cell get together with the theme of better understanding from basic cell mechanisms to latest Stem Cell breakthroughs!

Haval Shirwan, Ph.D. Executive Editor, Journal of Clinical & Cellular Immunology Dr. Michael and Joan Hamilton Endowed Chair in Autoimmune Disease Professor, Department of Microbiology and Immunology Director, Molecular Immunomodulation Program, Institute for Cellular Therapeutics, University of Louisville, Louisville, KY

Track01:Stem Cells

The most well-established and widely used stem cell treatment is thetransplantationof blood stem cells to treat diseases and conditions of the blood and immune system, or to restore the blood system after treatments for specific cancers. Since the 1970s,skin stem cellshave been used to grow skin grafts for patients with severe burns on very large areas of the body. Only a few clinical centers are able to carry out this treatment and it is usually reserved for patients with life-threatening burns. It is also not a perfect solution: the new skin has no hair follicles or sweat glands. Research aimed at improving the technique is ongoing.

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Track 02: Stem Cell Banking:

Stem Cell Banking is a facility that preserves stem cells derived from amniotic fluid for future use. Stem cell samples in private or family banks are preserved precisely for use by the individual person from whom such cells have been collected and the banking costs are paid by such person. The sample can later be retrieved only by that individual and for the use by such individual or, in many cases, by his or her first-degree blood relatives.

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Track 03: Stem Cell Therapy:

Autologous cells are obtained from one's own body, just as one may bank his or her own blood for elective surgical procedures. Adult stem cells are frequently used in medical therapies, for example in bone marrow transplantation. Human embryonic stem cells may be grown in vivo and stimulated to produce pancreatic -cells and later transplanted to the patient. Its success depends on response of the patients immune system and ability of the transplanted cells to proliferate, differentiate and integrate with the target tissue.

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Track 04: Novel Stem Cell Technologies:

Stem cell technology is a rapidly developing field that combines the efforts of cell biologists, geneticists, and clinicians and offers hope of effective treatment for a variety of malignant and non-malignant diseases. Stem cells are defined as totipotent progenitor cells capable of self-renewal and multilineage differentiation. Stem cells survive well and show stable division in culture, making them ideal targets for in vitro manipulation. Although early research has focused on haematopoietic stem cells, stem cells have also been recognised in other sites. Research into solid tissue stem cells has not made the same progress as that on haematopoietic stem cells.

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Track 05: Stem Cell Treatment:

Bone marrow transplant is the most extensively used stem-cell treatment, but some treatment derived from umbilical cord blood are also in use. Research is underway to develop various sources for stem cells, and to apply stem-cell treatments for neurodegenerative diseases and conditions, diabetes, heart disease, and other conditions.

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Track 06: Stem cell apoptosis and signal transduction:

Apoptosis is the process of programmed cell death (PCD) that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, chromosomal DNA fragmentation, and global mRNA decay. Most cytotoxic anticancer agents induce apoptosis, raising the intriguing possibility that defects in apoptotic programs contribute to treatment failure. Because the same mutations that suppress apoptosis during tumor development also reduce treatment sensitivity, apoptosis provides a conceptual framework to link cancer genetics with cancer therapy.

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Track 07: Stem Cell Biomarkers:

Molecular biomarkers serve as valuable tools to classify and isolate embryonic stem cells (ESCs) and to monitor their differentiation state by antibody-based techniques. ESCs can give rise to any adult cell type and thus offer enormous potential for regenerative medicine and drug discovery. A number of biomarkers, such as certain cell surface antigens, are used to assign pluripotent ESCs; however, accumulating evidence suggests that ESCs are heterogeneous in morphology, phenotype and function, thereby classified into subpopulations characterized by multiple sets of molecular biomarkers.

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Track 08: Cellular therapies:

Cellular therapy also called Cell therapy is therapy in which cellular material is injected into a patient, this generally means intact, living cells. For example, T cells capable of fighting cancer cells via cell-mediated immunity may be injected in the course of immunotherapy.

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Track 09: Stem cells and cancer:

Cancer can be defined as a disease in which a group of abnormal cells grow uncontrollably by disregarding the normal rules of cell division. Normal cells are constantly subject to signals that dictate whether the cells should divide, differentiate into another cell or die. Cancer cells develop a degree of anatomy from these signals, resulting in uncontrolled growth and proliferation. If this proliferation is allowed to continue and spread, it can be fatal.

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Track 10: Embryonic stem cells:

Embryonic stem cells have a major potential for studying early steps of development and for use in cell therapy. In many situations, however, it will be necessary to genetically engineer these cells. A novel generation of lentivectors which permit easy genetic engineering of mouse and human embryonic stem cells.

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Track 11: Cell differentiation and disease modeling:

Cellular differentiation is the progression, whereas a cell changes from one cell type to another. Variation occurs numerous times during the development of a multicellular organism as it changes from a simple zygote to a complex system of tissues and cell types. Differentiation continues in adulthood as adult stem cells divide and create fully differentiated daughter cells during tissue repair and during normal cell turnover. Some differentiation occurs in response to antigen exposure. Differentiation dramatically changes a cell's size, shape, membrane potential, metabolic activity, and responsiveness to signals. These changes are largely due to highly controlled modifications in gene expression and are the study of epigenetics. With a few exceptions, cellular differentiationalmost never involves a change in the DNA sequence itself. Thus, different cells can have very different physical characteristics despite having the same genome.

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Track 12: Tissue engineering:

Tissue Engineering is the study of the growth of new connective tissues, or organs, from cells and a collagenous scaffold to produce a fully functional organ for implantation back into the donor host. Powerful developments in the multidisciplinary field of tissue engineering have produced a novel set of tissue replacement parts and implementation approaches. Scientific advances in biomaterials, stem cells, growth and differentiation factors, and biomimetic environments have created unique opportunities to fabricate tissues in the laboratory from combinations of engineered extracellular matrices cells, and biologically active molecules.

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Track 13: Stem cell plasticity and reprogramming:

Stem cell plasticity denotes to the potential of stem cells to give rise to cell types, previously considered outside their normal repertoire of differentiation for the location where they are found. Included under this umbrella title is often the process of transdifferentiation the conversion of one differentiated cell type into another, and metaplasia the conversion of one tissue type into another. From the point of view of this entry, some metaplasias have a clinical significance because they predispose individuals to the development of cancer.

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Track 14: Gene therapy and stem cells

Gene therapy is the therapeutic delivery of nucleic acid polymers into a patient's cells as a drug to treat disease. Gene therapy could be a way to fix a genetic problem at its source. The polymers are either expressed as proteins, interfere with protein expression, or possibly correct genetic mutations. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient's cells instead of using drugs or surgery.

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Track 15: Tumour cell science:

An abnormal mass of tissue. Tumors are a classic sign of inflammation, and can be benign or malignant. Tomour usually reflect the kind of tissue they arise in. Treatment is also specific to the location and type of the tumor. Benign tumors can sometimes simply be ignored, cancerous tumors; options include chemotherapy, radiation, and surgery.

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Track 16: Reprogramming stem cells: computational biology

Computational Biology, sometimes referred to as bioinformatics, is the science of using biological data to develop algorithms and relations among various biological systems. Bioinformatics groups use computational methods to explore the molecular mechanisms underpinning stem cells. To accomplish this bioinformaticsdevelop and apply advanced analysis techniques that make it possible to dissect complex collections of data from a wide range of technologies and sources.

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The fields of stem cell biology and regenerative medicine research are fundamentally about understanding dynamic cellular processes such as development, reprogramming, repair, differentiation and the loss, acquisition or maintenance of pluripotency. In order to precisely decipher these processes at a molecular level, it is critical to identify and study key regulatory genes and transcriptional circuits. Modern high-throughput molecular profiling technologies provide a powerful approach to addressing these questions as they allow the profiling of tens of thousands of gene products in a single experiment. Whereas bioinformatics is used to interpret the information produced by such technologies.

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8th World Congress on Cell & Stem Cell Research

The success of the 7 Cell Science conferences series has given us the prospect to bring the gathering one more time for our 8thWorld Congress 2017 meet in Orlando, USA. Since its commencement in 2011 cell science series has perceived around 750 researchers of great potentials and outstanding research presentations around the globe. The awareness of stem cells and its application is increasing among the general population that also in parallel offers hope and add woes to the researchers of cell science due to the potential limitations experienced in the real-time.

Stem Cell Research-2017has the goal to fill the prevailing gaps in the transformation of this science of hope to promptly serve solutions to all in the need.World Congress 2017 will have an anticipated participation of 100-120 delegates from around the world to discuss the conference goal.

History of Stem cells Research

Stem cells have an interesting history, in the mid-1800s it was revealed that cells were basically the building blocks of life and that some cells had the ability to produce other cells. Efforts were made to fertilize mammalian eggs outside of the human body and in the early 1900s, it was discovered that some cells had the capacity to generate blood cells. In 1968, the first bone marrow transplant was achieved successfully to treat two siblings with severe combined immunodeficiency. Other significant events in stem cell research include:

1978: Stem cells were discovered in human cord blood 1981: First in vitro stem cell line developed from mice 1988: Embryonic stem cell lines created from a hamster 1995: First embryonic stem cell line derived from a primate 1997: Cloned lamb from stem cells 1997: Leukaemia origin found as haematopoietic stem cell, indicating possible proof of cancer stem cells

Funding in USA:

No federal law forever did embargo stem cell research in the United States, but only placed restrictions on funding and use, under Congress's power to spend. By executive order on March 9, 2009, President Barack Obama removed certain restrictions on federal funding for research involving new lines of humanembryonic stem cells. Prior to President Obama's executive order, federal funding was limited to non-embryonic stem cell research and embryonic stem cell research based uponembryonic stem celllines in existence prior to August 9, 2001. In 2011, a United States District Court "threw out a lawsuit that challenged the use of federal funds for embryonic stem cell research.

Members Associated with Stem Cell Research:

Discussion on Development, Regeneration, and Stem Cell Biology takes an interdisciplinary approach to understanding the fundamental question of how a single cell, the fertilized egg, ultimately produces a complex fully patterned adult organism, as well as the intimately related question of how adult structures regenerate. Stem cells play critical roles both during embryonic development and in later renewal and repair. More than 65 faculties in Philadelphia from both basic science and clinical departments in the Division of Biological Sciences belong to Development, Regeneration, and Stem Cell Biology. Their research uses traditional model species including nematode worms, fruit-flies, Arabidopsis, zebrafish, amphibians, chick and mouse as well as non-traditional model systems such as lampreys and cephalopods. Areas of research focus include stem cell biology, regeneration, developmental genetics, and cellular basis of development, developmental neurobiology, and evo-devo (Evolutionary developmental biology).

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UAS Major Universities which deals with Stem Cell Research

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Norwegian Center for Stem Cell Research

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Adult Stem Cells: The Best Kept Secret In Medicine | The …

By Adult Stem Cells

5190395

Stem cell therapies and their lifesaving results are arguably the best kept medical secret. Stem cells are currently being used in several thousand FDA-approved clinical trials, are treating tens of thousands of patients every year, and cumulatively over 1.5 million people have been treated to date. Yet these numbers, and the lifesaving results from stem cells for dozens of conditions, are unknown to most. Why the information blackout? Perhaps for lack of an adjective.

You see, those heartening numbers are all due to adult stem cells. Long ignored by the media and disparaged even by many in the scientific community, adult stem cells those not dependent on the destruction of embryos are the true gold standard for stem cells, especially when it comes to treating patients.

A recent New York Times piece provides a perfect example of the disinformation campaign. Early on, the author discusses the theoretical nature of stem cell treatments and bemoans the fact that progress is slow, almost all the research is still in mice or petri dishes, and The very few clinical trials that have begun are still in the earliest phase.

Whether through ignorance or bias, the sole focus is clearly on embryonic stem cells. Such writing, however, serves to confuse, not illuminate, the facts about stem cells and therapies.

Contrary to the blinkered portrayal of stem cells in the article, there are in fact almost 3,500 ongoing or completed clinical trials using adult stem cells, listed in the NIH/FDA-approved database. Moreover, large numbers of patients have been treated with adult stem cells. In 2012 there were almost 70,000 patients treated around the globe in that year alone, and almost 20,000 patients treated in just the U.S. in 2014. Cumulatively, its been documented that as of December 2012, there had already been over one million adult stem cell transplants. This means that now, over 1.5 million patients have had their lives saved and health improved by adult stem cell transplants.

Our focus is indeed on adult stem cells both because they are efficacious for patients, as well as because adult stem cells are derived without the destruction of the stem cell donor, unlike embryonic stem cells and fetal stem cells. Both positions are based on the facts of biology.

The New York Times Kolata criticizes various stem cell clinics within the U.S., primarily via a paper by two long-time proponents of embryonic stem cells (though this is not disclosed in the article or in the paper), but paints a broad-brush across clinics operating legally and ethically as well as the shady operators. It then juxtaposes the critique of U.S. stem cell clinics with the tragic story of a patient who traveled to three different overseas clinics to receive stem cell injections and developed a growing mass of cells on his spine from at least one of the injections. The implied warning is that all U.S. adult stem cell clinics are using similar methods, and, by extension, their patients may experience similar problems. Indeed, many clinics are offshore to avoid FDA rules, but yet again the article drops adjectives and sows confusion. The New England Journal of Medicine source on the case notes that the patient supposedly received proliferating cells including embryonic and fetal stem cells. Certainly all clinics should operate within appropriate ethical and legal boundaries and patients should receive all information, including published background and whether the cells being used are adult, fetal, or embryonic; this is simply a matter of getting full informed consent. But fearmongering and misinformation help neither the patients nor the science.

The stem cell science deniers continue to denigrate adult stem cells, denying their successes or even at times their existence by dropping the necessary, descriptive adjective. But for patients, adult stem cells are the true gold standard for stem cells. The hope of adult stem cells is being realized right now, for thousands of people around the globe. Those stories, those doctors, those patients who have been helped by adult stem cell treatments, deserve to be heard. People like Cindy Schroeder who thought she was given a death sentence when she was diagnosed with multiple myeloma. But Cindys doctor was informed on the facts of modern medicine, and was able to inform Cindy and her family that there was hopefrom adult stem cells. Over a year after her stem cell treatment, Cindy leads a full, active life and her family is closer than ever. Her story, like that of thousands of others, is not theoretical; its real adult stem cell science.

Dr. David A. Prentice, VP & Research Director for the Charlotte Lozier Institute as well as Adjunct Professor of Molecular Genetics at the John Paul II Institute, The Catholic University of America, and an Advisory Board Member for the Midwest Stem Cell Therapy Center.

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Adult Stem Cells: The Best Kept Secret In Medicine | The ...

Inducible Site-Specific Recombination in Neural Stem …

By Adult Stem Cells

Genesis. Author manuscript; available in PMC 2009 Jul 10.

Published in final edited form as:

PMCID: PMC2708938

NIHMSID: NIHMS128325

Department of Developmental Biology and Kent Waldrep Foundation Center for Basic Neuroscience Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas

Jian Chen and Chang-Hyuk Kwon contributed equally to this work.

To establish a genetic tool for manipulating the neural stem/progenitor cell (NSC) lineage in a temporally controlled manner, we generated a transgenic mouse line carrying an NSC-specific nestin promoter/enhancer expressing a fusion protein encoding Cre recombinase coupled to modified estrogen receptor ligand-binding domain (ERT2). In the background of the Cre reporter mouse strain Rosa26lacZ, we show that the fusion CreERT2 recombinase is normally silent but can be activated by the estrogen analog tamoxifen both in utero, in infancy, and in adulthood. As assayed by -galactosidase activity in embryonic stages, tamoxifen activates Cre recombinase exclusively in neurogenic cells and their progeny. This property persists in adult mice, but Cre activity can also be detected in granule neurons and Bergmann glia at the anterior of the cerebellum, in piriform cortex, optic nerve, and some peripheral ganglia. No obvious Cre activity was observed outside of the nervous system. Thus, the nestin regulated inducible Cre mouse line provides a powerful tool for studying the physiology and lineage of NSCs.

Keywords: Cre-ERT2, nestin, neural stem cells, tamoxifen, transgenic mouse, recombination

The recognition that the adult brain retains stem cells (NSCs) has fundamentally changed our view of brain plasticity (Lie et al., 2004; Ming and Song, 2005; Zhao et al., 2008). It also raises the hope of cell replacement therapy for neurodegenerative disease (Lie et al., 2004). Adult neurogenesis in the subventricular zone (SVZ) of the lateral ventricles serves to replenish olfactory bulb (OB) interneurons via the rostral migratory stream (RMS). In the dentate gyrus, neurogenesis in the subgranular layer (SGL) generates synaptically active granule neurons and has been implicated in learning, memory and mood disorders in rodents (Li et al., 2008; Ming and Song, 2005; Zhang et al., 2008; Zhao et al., 2008). The development of conditional mutant alleles using the Cre/loxP system has permitted circumvention of early lethality observed when many genes are mutated by traditional knockout, thus offering the opportunity to study gene function with spatial control (Mak, 2007). A further refinement of this technology has been the development of inducible Cre transgenes that permit temporal control of gene recombination and inactivation (Feil et al., 1997; Hayashi and McMahon, 2002). Fusion of the Cre recombinase protein with a modified estrogen receptor ligand-binding domain (ERT2) causes sequestering of the fusion protein in the cytoplasm where it cannot mediate loxP recombination. Application of estrogen or estrogen analogs, however, causes translocation of the Cre-ERT2 fusion protein to the nucleus where recombination can then be achieved.

To achieve temporal ablation of genes in the neural stem cell lineage, we have constructed a tamoxifen-inducible Cre transgene that is regulated by the neurogenic lineage specific promoter/enhancer of the nestin gene. Nestin is an intermediate filament protein specifically expressed in neural stem/progenitor cells in both developing central nervous system and adult brain. The regulatory element driving neural-specific nestin expression has been mapped to the second intron of the nestin gene (Lendahl et al., 1990; Zimmerman et al., 1994). As detailed in our studies, we show that the transgene is silent in the absence of estrogen analog. Upon activation, the expression is robust and recombination is elicited primarily in the principal neurogenic niches. Additional expression is confined to the cerebellum, certain peripheral nerves, and to the piriform cortex, a potentially novel site of neurogenesis.

The Cre-ERT2 cDNA was placed under the control of a 5.6 kb rat nestin 5 regulatory element and followed by the 668 bp of inversed nestin second intron (). Six transgenic lines were obtained after pronuclear injection and four underwent germline transmission. To assay Cre recombinase activity after induction, we crossed the CreERT2 lines with Rosa26-stop-lacZ (Rosa26lacZ) reporter mice. The Rosa26lacZ mice require Cre-mediated recombination for -galactosidase gene activation due to a stop cassette flanked by loxP sites upstream of the lacZ gene. To assess inducibility of the Cre transgene, sunflower oil vehicle (150 l) or the estrogen analog tamoxifen (1 mg) was injected into pregnant mice at embryonic day 12.5 (E12.5) and the embryos were dissected out at E14.5 for whole mount X-gal staining. In a Rosa26lacZ reporter background, exposure of the four transgenic lines to tamoxifen revealed that only two of the lines (Line 8 and Line 73) exhibited recombination activity ( and not shown). Moreover, comparison of Cre activity upon induction was similar although Line 8 was leaky, having minor but detectable Cre activity in the absence of tamoxifen. In contrast, Line 73 (Nes73-CreERT2) showed no signs of Cre activity in the absence of tamoxifen and the blue X-gal staining was found predominantly in embryonic brain and spinal cord where most nestin-positive neural progenitors are located ().

Transgene construct and tamoxifen inducibility. (a) Structure of the Nestin-CreERT2 transgene consisting of the rat nestin promoter/enhancer, cDNA encoding the CreERT2 fusion protein and inversely oriented Nestin second intron. (b) Transgene induction ...

The temporal control of Cre activity allowed us to induce Cre-mediated recombination for the purpose of tracing NSCs and their progeny at various time points. The pattern observed upon embryonic induction closely reflected the course of brain development. Tamoxifen induction at E13.5 labeled almost the entire cortex in the forebrain as well as the entire cerebellum including neurons and glia (). This coincides with the initiation of neural progenitor migration that contributes to different cortical layers in embryonic neural development (Sun et al., 2002). Induction at E17.5, when neurogenesis in the forebrain reaches completion, resulted in labeling of only the outer most layers of the cortex (), which stands in line with the inside-out pattern of cortex layer formation (Sun et al., 2002). Additionally, the thalamus and hindbrain were labeled at this time point. In the neonatal mouse brain, there is persistent mild but widespread lacZ activity, indicative of residual but rare progenitor cells throughout the parenchyma (). The most active neurogenic region at this time is the cerebellum (Herrup and Kuemerle, 1997), which showed intense lacZ staining following induction at E17.5 through P7 (). Mouse cerebellum development is considered to be complete by 3 weeks after birth, however our Nes73-CreERT2;Rosa26lacZ mice showed strong Cre activity in the anterior part of cerebellum when induced 4 and 8 weeks after birth (, and ; and see below). Nonetheless, in the anterior brain, by 4 weeks of age the SVZ and SGL are the most neurogenic regions as assayed by tamoxifen-induced Cre activity ().

Novel Cre activity. Nes73-CreERT2;Rosa26lacZ mice were treated with tamoxifen at 4 weeks of age and analyzed at 8 weeks (ac, eh, left and right panel of i). Abundant -Gal expression was detected in the anterior part of cerebellum ...

Adult NSCs modify their gene expression as they migrate and differentiate. In the SVZ, glial fibrillary acidic protein (GFAP) positive cells are considered to be stem cells (Doetsch et al., 1999). When differentiation starts and neuronal fate of the progenitor cells has been specified, cells begin to express doublecortin (DCX) and migrate into the OB through the RMS to finally become NeuN-positive mature neurons (Doetsch et al., 1999; Ming and Song, 2005). To determine the sites of primary Cre recombinase activity, we examined the SVZ of 4-week-old Nes73-CreERT2;Rosa26lacZ mice 48 h after a short pulse of tamoxifen, since both GFAP-positive neural stem cells and some transient amplifying progenitor cells express nestin. X-gal staining followed by immunohistochemistry (IHC) with GFAP or DCX antibody revealed that the majority of Cre activity resides in GFAP-positive SVZ cells close to the lateral ventricle, with only rare DCX-positive SVZ or RMS cells showing recombination (). This was further confirmed using an estrogen receptor antibody to show double labeling of Cre-ERT2-positive cells with the stem cell marker GFAP, and with S100, a marker of radial glia-derived ependymal cells (Supp. Info. Fig. 1) (Spassky et al., 2005). These studies indicate that the primary site of tamoxifen-activated Cre recombinase is the GFAP-positive, SVZ stem cell population.

Cre activity in adult NSC niches and migration targets. (a) Representative X-gal stained brain sections from mice 48 h after two tamoxifen administrations at P28 (12-h interval). X-gal signal was mainly restricted to SVZ (a1), with little or no signal ...

To measure the efficiency of tamoxifen-induced recombination in our Nes73-CreERT2 mice, we crossed them with the Rosa26YFP reporter line to generate Nes73-CreERT2;Rosa26YFP mice and then induced these mice with tamoxifen at 4 weeks of age. We then harvested brain sections from the induced mice at 6 weeks of age, and performed immunofluorescent double-labeling with GFP and Sox2 antibodies (Supp. Info. Fig. 2). The percentage of GFP/Sox2 double-positive cells divided by the number of Sox2 positive cells in the SVZ was used to determine recombination efficiency. This quantification analysis revealed that 75 4% of Sox2-positive cells in the SVZ have been targeted 2 weeks after a 5-day tamoxifen induction.

To further study the dynamics of stem/progenitor cell migration and differentiation, Nes73-CreERT2;Rosa26lacZ mice were induced at 4 weeks of age and examined by X-gal staining 2 or 4 weeks later ( and ). The dynamics of Cre-active cells in the hippocampus over time was not very dramatic (), however in the SVZ, an increase in the number of Cre active cells in an expanded ventricular area was evident 4 weeks after induction (). These results suggest a precursor-progeny relationship in which, after 2 weeks of induction, a significant number of new progenitor cells have been generated by stem cells and are beginning to disperse from the SVZ. Similarly, in the OB 2 weeks after induction, the X-gal positive cells were confined to a central cluster, whereas 4 weeks postinduction the cells were dispersed throughout the OB (). We interpret this result to indicate that at 2 weeks postinduction, cells are just arriving to the OB via the RMS and are confined to this central area, whereas at 4 weeks postinduction, these labeled cells have now dispersed throughout the OB. A similar, although more restricted, migration was also observed in hippocampus, where -Gal and NeuN double-positive neurons first appear close to the SGL 2 weeks after induction but by 4 weeks postinduction have migrated deeper into the granular layer ().

To explore the identity of the Cre-active cells, immunofluorescent double labeling was used to characterize Nes73-CreERT2;Rosa26lacZ mice 4 weeks after induction (). -Gal immunoreactivity was found in nestin and GFAP-positive neural stem/progenitor cells in the SVZ and SGL (). In the anterior part of the SVZ and SGL, DCX-positive neural progenitors also showed Cre activity (). In addition, a majority of the cells in the RMS express both -Gal and DCX (). Furthermore, NeuN-positive mature neurons that also retained -Gal immunoreactivity could be found in the HP and OB (). A small number of GFAP-positive astrocytes in the OB and the corpus callosum (CC) also expressed the reporter gene -Gal (), indicating the presence of Cre activity in multiple cell types in the NSC lineage. This result is consistent with recent quantitative lineage tracing studies (Lagace et al., 2007).

The significant amount of Cre activity induced in anterior cerebellum of adult mice was unexpected (). shows a representative eight-week-old brain from a mouse that was induced with tamoxifen at 4 weeks of age. The -Gal positive cells were mostly NeuN-positive inner granular layer (IGL) granule cells and Bergmann glia that extend long processes to the surface of the cerebellum (). Consistent with previous reports that Bergmann glia express NSC markers such as nestin and Sox2 (Mignone et al., 2004; Sottile et al., 2006), we found that Cre-active Bergmann glia also expressed the NSC marker nestin (). However, the Cre-ERT2 fusion transgene was also expressed in some Sox2-negative cells in the IGL (, middle panel), suggesting potential aberrant expression of the Nestin-CreERT2 transgene. Mild but reproducible tamoxifen-induced Cre activity was also observed in the piriform cortex (), which has also been reported to be a potential neurogenic region (Pekcec et al., 2006). We next assessed tamoxifen-induced Cre activity in other regions using whole mount X-gal staining, and found that the dorsal root ganglia (DRG) but not the spinal cord showed Cre activity (). Histologic examination revealed that less than half of the DRG neurons undergo Cre-mediated recombination (). In addition, Cre activity was detected in the optic nerve and trigeminal ganglia in mice induced at neonatal (, middle panel) or adult stages (, right panel). Collectively these data indicate that the nestin promoter/enhancer employed to generate this tamoxifen inducible transgene, exhibits remarkable fidelity to the endogenous neural expression with only a few potential sites of discrepancy.

Detailed analysis of traditional Nestin-Cre transgenic lines has revealed Cre activity outside the CNS, for example, in the kidney and in somite-derived tissues (Dubois et al., 2006). To determine whether Cre activity in the Nes73-CreERT2 mice was restricted to the nervous system, Nes73-CreERT2;Rosa26lacZ mice were induced for 5 days starting at P0 and analyzed at 8 weeks of age by whole-mount X-gal staining of internal organs including the heart, lung, liver, thymus, spleen, kidney, pancreas and stomach. With the exception of the esophagus, where neonatal but not adult exposure to tamoxifen induced Cre activity (, Supp. Info. Fig. 3) and stomach, where spontaneous lacZ activity is present in controls (, Supp. Info. Fig. 3) (Kwon et al., 2006), we found no evidence of obvious reporter expression in the absence or presence of tamoxifen (see ).

Cre activity is not observed in internal organs. Nes73-CreERT2;Rosa26lacZ mice were treated with vehicle (Veh) or tamoxifen (Tmx) at P0 for 5 days. Different organs were then dissected out at 8 weeks and subjected to whole mount X-gal staining. Endogenous ...

The rediscovery of neurogenesis in the adult brain has led to reawakened interest in the role of new neurons in the mature brain. The SVZ is a major site of neurogenesis for OB interneurons, although emerging evidence suggests additional roles. In the hippocampus, neurogenesis has been implicated in mood modulation and in learning and memory (Li et al., 2008; Lie et al., 2004; Zhao et al., 2008). On the dark side, stem/progenitor cells in the CNS have been implicated as the source of glioblastoma (Kwon et al., 2008; Sanai et al., 2005; Zhu et al., 2005). Specific ablation or activation of genes implicated in hippocampal function and in glioma can be achieved with our tamoxifen-inducible Cre transgene and we have developed successful models of both SVZ stem/progenitor cell-dependent induction of glioma and hippocampal stem/progenitor cell-dependent antidepressant insensitive mice using this tamoxifen-inducible Cre mouse line (Li et al., 2008; Llaguno et al., submitted).

Still, there is much to be learned about the precise role of neural stem cells in normal brain function and in associated pathologies. For example, in this report we describe novel sites of nestin-Cre recombinase activity. Whether this activity identifies previously undetected sites of neurogenesis or simply ectopic Cre expression remains to be rigorously determined. Of note, a second, independently derived transgenic line, Nes8-CreERT2, shows a similar pattern of inducible expression (data not shown) leading us to favor the conclusion that the expression outside the SVZ and SGZ is not due to position effects at the site of transgene insertion but rather is a reflection of the properties of the transgenic construct. Stem cells have been isolated from neonatal cerebellum and they are reported to be prominin/CD133-positive and Math1-negative (Klein et al., 2005; Lee et al., 2005). We observe Cre activity in the cerebellum from E17.5 through 8 weeks of age. Although diminishing over time, a clear gradient is observed that becomes progressively more anterior. The lacZ positive cells resulting from activation of the Rosa26 reporter possess the characteristic morphology of granule cells. In adult cerebellum, the Bergmann glia retain a morphology reminiscent of radial glia which can generate neurons and adult NSCs during brain development (Gotz and Barde, 2005; Merkle et al., 2004). In addition, Bergmann glia still express stem cell markers such as Sox2 and nestin (Mignone et al., 2004; Sottile et al., 2006). On the other hand, only rarely have cells with BrdU incorporation been observed in adult cerebellum, even after growth factor infusion (Grimaldi and Rossi, 2006). We also found that a number of cells in the anterior cerebellum targeted 2 days after acute tamoxifen administration were positive for NeuN but not GFAP or nestin (Supp. Info. Fig. 4), suggesting that the cre activity in the IGL was more likely due to promoter leakiness (Supp. Info. Fig. 4). Further study is needed to resolve this issue.

A series of similar inducible Nestin-Cre transgenes has recently been reported, although the extent of expression over time and expression outside the nervous system was not described (Supp. Info. Table 1) (Balordi and Fishell, 2007; Burns et al., 2007; Imayoshi et al., 2006; Kuo et al., 2006; Lagace et al., 2007). Eisch and co-workers recently described a tamoxifen-inducible Cre transgenic mouse line with no obvious Cre activity in the cerebellum upon tamoxifen induction (Lagace et al., 2007). The fact that our transgenic construct included only intron 2 of the nestin gene whereas their construct contained nestin exons 13 could account for this discrepancy (Zimmerman et al., 1994). It is possible that our more limited nestin construct might lack cerebellar-specific repressor sequences. Another potentially significant variation is the use of a Rosa26lacZ reporter line versus the Rosa26YFP reporter used by Lagace et al. (2007). Both the sensitivity of the reporter and perhaps the recombinogenic efficiency could in principle differ, leading to these discrepancies. We also observe Cre activity in the adult piriform cortex. This is in accordance with previous reports of BrdU incorporation in this region, leading to the suggestion of additional neurogenic niches (Pekcec et al., 2006).

We examined our mice for leakiness as well as for inducible transgene expression in the peripheral nervous system (PNS) and multiple organs. In contrast to many other Nestin reporter transgenic mice (Day et al., 2007; Dubois et al., 2006; Gleiberman et al., 2005; Li et al., 2003; Ueno et al., 2005), we found no evidence of obvious leakiness or of inducible transgene activation outside the CNS except in the PNS, where inducible expression was found both in the DRG and trigeminal ganglion, and in the esophagus. It is possible that our Nestin-CreERT2 transgene has a more restricted expression pattern or that the tamoxifen induction efficiency is lower in certain tissues. In addition, whole mount X-gal staining of the organs makes it difficult to capture rare Cre-positive cells if they do exist. DRG have been used to culture neurospheres (Li et al., 2007), and it will be of interest to determine whether our transgene is active in these progenitor cells, which would provide supportive evidence for the existence of additional neural stem/progenitor niches. Subsequent detailed lineage tracing of the Cre expressing cells will more clearly address this issue.

A 2.0 kb fragment of CreERT2 and SV40 polyA sequence of the pCre-ERT2 vector (Feil et al., 1997) were amplified using a PCR technique that also generated 5 Not1 and 3 Spe1 sites. After enzymatic digestion, purified fragment was ligated to an 8.9 kb fragment from pNerv (Panchision et al., 2001; Yu et al., 2005) digested with Not1 and Xba1. The resulting pNes-CreERT2 construct contains a 5.6 kb rat nestin 5 genetic element from pNerv, a 2.0 kb CreERT2 and SV40 polyA sequence from pCre-ERT2 and a 668 bp of reversed second intron of rat nestin from pNerv (). After Sal1 digestion, an 8.3 kb band was purified and microinjected into the pronuclei of fertilized eggs from B6D2F1 mice. Among 28 pups born after two rounds of transgenic injection, six contained the transgene, and four of them transmitted to germline. Rosa26lacZ mice were obtained from Jackson Laboratories (Bar Harbor, ME), Rosa26YFP mice were kindly provided by Dr. Jane Johnson. All the mice were maintained in a mixed genetic background of C57BL/6, SV129 and B6/CBA. Nestin73-CreERT2; Rosa26lacZ mice were generated by crossing male Nestin-CreERT2 mice with female Rosa26lacZ mice. Genotyping of the mice was performed as described previously (Kwon et al., 2006). All mouse protocols were approved by the Institutional Animal Care and Research Advisory Committee at the University of Texas Southwestern Medical Center.

Tamoxifen (Sigma-Aldrich, St. Louis, MO) was dissolved in a sunflower oil (Sigma-Aldrich, St. Louis, MO)/ethanol mixture (9:1) at 6.7 mg/ml. For initial screening of the embryonic induction of the transgenic lines, 150-l tamoxifen (1 mg) or vehicle (sunflower oil/ethanol mixture only) was injected intraperitoneally into pregnant mice at embryonic day E12.5 (E12.5 hereafter). Embryos were dissected out 2 days later and subjected to X-gal staining. For in utero induction, 150-l tamoxifen (1 mg) or vehicle was injected intraperitoneally into pregnant mothers at E13.5 or E17.5, and pups were analyzed 1 month after birth. For neonatal induction, 12.5-l tamoxifen (83.5 mg/kg body weight) or vehicle per gram of mouse body weight was injected into lactating mothers (tamoxifen can be delivered to pups through the mothers milk) at P0 or P7, once a day for 5 days and the pups were analyzed 4 weeks after the first induction. For induction in adult mice, 12.5-l tamoxifen (83.5 mg/kg) or vehicle per gram of body weight was injected intraperitoneally into 4- or 8-week-old mice twice a day for five consecutive days and then analyzed 2 or 4 weeks after the first induction.

Mice were dissected and perfused as previously described (Kwon et al., 2006). For whole mount X-gal staining, the embryos or organs were carefully dissected out, washed with phosphate-buffered saline (PBS), and then fixed in 2% (w/v) paraformaldehyde (PFA; in PBS) for 1 h at 4C. Postnatal brains were postfixed in 2% PFA overnight (O/N) at 4C, embedded in 2.5% chicken albumin sagittally or coronally, and then cut into 50-m thick sections by vibratome (Leica, Nussloch, Germany). Every fifth sagittal section or 12th coronal section was chosen to perform X-gal staining and comparable sections were selected for further immunostaining according to the X-gal staining result. X-gal staining of organs and sections was performed as described (Kwon et al., 2006).

Four Nestin73-CreERT2;Rosa26YFP mice were induced at 4 weeks of age as described above and perfused with 2% PFA at 6 weeks of age. The brains were dissected out, postfixed in 4% PFA O/N at 4C, processed and embedded in paraffin blocks. Five-m thick sagittal sections were cut until the lateral ventricle was gone. H&E staining was performed on every fifth slide to determine comparable sections. Every 10th of comparable sections was subjected to GFP (Aves Labs, Tigard, OR) and Sox2 (Chemicon, Temecula, CA) immunofluorescence staining, and three random regions of the frontal SVZ of each section were selected for counting. The efficiency was determined by the percentage of GFP (mean 203)/Sox2 (mean 270) double-positive cells out of the total Sox2-positive cells in SVZ.

Free-floating immunofluorescence staining was performed on 50-m thick sections. Antibodies used for the staining were against -galactosidase (ICN, Aurora, OH), GFAP, nestin (BD Biosciences, Bedford, MA), doublecortin (Santa Cruz Biotechnology, Santa Cruz, CA), NeuN (Chemicon, Temecula, CA), Mash1 (BD Biosciences, Bedford, MA), S100 (Sigma-Aldrich, St. Louis, MO). Alexar-488 or Alexar-555 conjugated goat anti-mouse or anti-rabbit (Molecular Probes, Eugene, OR) and Cy2 or Cy3 donkey anti-goat, anti-rabbit antibodies (Jackson Immunoresearch, West Grove, PA) were used to visualize primary antibody staining. Images were taken on a Zeiss LSM 510 confocal microscope (Carl Zeiss, Jena, Germany). For ER and Sox2 staining, 5-m thick paraffin sections were first stained with estrogen receptor antibody (Lab Vision, Fremont, CA) and visualized by DAB substrate with nickel solution (Vector Laboratories, Burlingame, CA). The slides were then washed with PBS three times, stained with Sox2 antibody (Chemicon, Temecula, CA), and visualized by Vector NovaRED (Vector Laboratories, Burlingame, CA). Images were taken with a Nikon 2000 CCD camera (Nikon, Japan). All images were assembled using Adobe Photoshop CS and Illustrator CS (Adobe Systems Incorporated, San Jose, CA).

We thank Steven Kernie for providing pNerv plasmid, Jane Johnson and Frank Costantini for providing Rosa26YFP mice, Steven McKinnon, Shirley Hall, and Linda McClellan for technical assistance, Renee McKay for reading the manuscript, and Jane Johnson, James Battiste, Jing Zhou, and Yun Li for discussion and suggestions.

Additional Supporting Information may be found in the online version of this article.

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Inducible Site-Specific Recombination in Neural Stem ...

First stem cell treatment for human administered in Atlanta …

By Stem Cell Clinics

Taking a landmark step, Atlanta doctors have injected millions of embryonic stem cells into a partially paralyzed patient, treating a human for the first time in the U.S. with the controversial research, officials said Monday.

The medical procedure took place Friday at an unknown local hospital and the person, who was not identified, later entered the Shepherd Center, which specializes in brain and spinal cord injuries, for rehabilitation.

While supporters hailed the treatment as a monumental medical advance, others derided it as a moral atrocity. There was some irony in Atlanta being selected as the first American site for embryonic stem cell treatment, considering there have been several legislative proposals previously calling for a research ban. Clearly there was a divide when the news was revealed.

This is a big deal for Atlanta, said Steve Stice, director of the University of Georgias Regenerative Bioscience Center. One of my sons roommates at UGA [who is paralyzed] could be helped by this eventually.

Atlanta was chosen for the initial clinical trial because of the citys reputation for cutting-edge research in spinal-cord injuries and the Shepherd Centers advanced rehabilitation center, said Anna Krassowska, spokeswoman for Geron Corp. of Menlo Park, Calif., which is sponsoring the research. The stem cell treatment could be offered to 10 patients at seven sites nationwide, with Atlanta receiving more patients, Krassowska said.

This clinical trial represents another step forward in Shepherd Centers involvement in an attempt to find a cure for paralysis in people with spinal cord injury, Dr. David Apple, the center leader for the stem cell procedure, said in a statement.

The Shepherd Center will play a large role in judging the success of the trial by closely monitoring whether the patient regains any sensation or movement.

If successful, the treatment could would mark a medical milestone and elevate Atlantas stature in the scientific community, providing a breakthrough in dealing with spinal cord injuries.

Stem cell research has drawn opposition because the process of harvesting the cells destroys human embryos, which some liken to an abortion. However, researchers see a medical need for the work, noting that embryonic stem cells can morph into any type of cell.

Georgians retain strong opinions on both sides of the issue, particularly in the political ranks.

Among the top candidates in the governors race, Democrat Roy Barnes supports stem cell research and Republican Nathan Deal opposes it.

I believe our state must embrace the necessity of stem cell and other types of bio-tech research as being essential to the development of a vibrant economy, Barnes said,

Deal, according to his spokesman Brian Robinson, supports research that does not include the creation of life for the purpose of destroying it.

State Representative James Mills, R-Gainesville, who sponsored a bill that allows parents to adopt human embryos, also spoke against the use of embryonic stem cells in research.

In a case where a childs life is taken in order for research to be done, I am opposed to that, he said.

The executive director of Georgia Right to Life, Nancy Stith, said she was shocked to learn the federal government had allowed the trial to proceed. We are very much heart-broken, disappointed and concerned that it is happening, she said.

Her organization supports stem cell technologies but is opposed to the research because it destroys human life.

When is it ethical that a human has to die to benefit someone else? Stith said. We believe never.

Stem cell research occurs at several Georgia institutions, including Georgia Tech, Emory University and UGA, and this particular procedure could bring more clinical trials to the area, UGAs Stice said.

Stice said embryonic stem cells have been tested in animals and he has heard of some clinics worldwide offering human therapies, but this clinical trial marks the first time the work has been approved by a government and carefully evaluated. The Food and Drug Administration gave its approval in July.

In this particular clinical trial, stem cells are converted into nerve cells that are injected into the damaged area of the spinal cord. It is hoped the stem cells will help repair nerve cells around the damaged area, potentially restoring movement.

The Geron Corp. said some paralyzed rats used in research regained the ability to walk, but otherwise was restrained in offering its expectations.

The Atlanta patient needed to be someone who was injured within the past 14 days and was between the ages of 18 to 65. The patient was injured in the middle section of the spine and was paralyzed from the waist down. No other information on the patient was released.

The surgery went well, said Krassowska.

The future of federal funding for embryonic stem cell research remains in question. A federal judge ruled in August that President Barack Obamas expansion of the research violated a federal law prohibiting taxpayer money be used for research that involves the destruction of human embryos. Geron did not receive federal funding for its work.

Company officials said they couldnt put a timetable on the process.

We just dont know, Krassowska said. This has never been done before in humans.

The Associated Press, BBC and the Washington Post contributed to this article.

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First stem cell treatment for human administered in Atlanta ...

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