Daniel Kraft on Singularity 1 on 1 (part 2) – Video

31-01-2012 19:41 http://www.singularityweblog.com This morning I interviewed Daniel Kraft for Singularity 1 on 1. I met Dr. Kraft at Singularity University where he is the Medicine and Neuroscience Chair and executive director of the FutureMed Program. Daniel is one of those people with an incredibly diverse spectrum of talents and interests for he is not only a medical doctor and oncologist but also an inventor, a technology and space enthusiast, an entrepreneur and an F-16 flight surgeon. During our conversation we discuss a variety of topics such as: Daniel's early interest and talent in technology and science; his original fascination with the Apollo Space program and eventual participation in International Space University; his passion for flying and being a pilot; his medical education and personal journey to becoming a faculty member at Singularity University; his desire to be an instigator, connector and motivator of innovation; the story behind as well as the purpose and structure of the FutureMed program; bone marrow harvesting, regenerative medicine and stem cell research; longevity and the future of medicine and health care; his greatest inspiration and concerns about the field of medicine and his belief that one doesn't have to be a doctor to improve health care.

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Daniel Kraft on Singularity 1 on 1 (part 2) - Video

ThermoGenesis Provides Update on Res-Q® Clinical Evaluations at Leading Stem Cell Therapy Conference

 

RANCHO CORDOVA, Calif., Feb. 1, 2012 /PRNewswire/ -- ThermoGenesis Corp. (NASDAQ: KOOL - News), a leading supplier of innovative products and services that process and store adult stem cells, today provided updates on two clinical evaluations involving its Res-Q® 60 BMC (Res-Q) system, a point-of-care platform designed for the preparation of cell concentrates from bone marrow.

Speaking at the Seventh International Conference on Cell Therapy for Cardiovascular Disease, Vijay Kumar, Ph.D., the Company's principal scientist and Manager of Research, said the initial data are encouraging for patients being treated in clinical evaluations for Critical Limb Ischemia (CLI) and long bone fractures with concentrates prepared by the Res-Q.

The studies covered in Kumar's presentation included:

A clinical evaluation in India co-sponsored by ThermoGenesis and Totipotent SC, the Company's distributor for the Res-Q in India. Ten of 15 planned patients with advanced CLI have been enrolled to date with the primary endpoints of safety and rate of limb salvage at one year. Kumar reported a statistically significant improvement in ankle brachial index, six-minute walk test, and rest pain though further data remain to be collected. The lead investigator for this study is Dr. Suhail Bukhari of Fortis Escorts Heart Institute and Research Center in New Delhi. A clinical evaluation that has enrolled sixteen of 20 planned patients with a non-union or delayed union fracture of a long bone who have undergone composite grafting with autologous bone marrow cell concentrate to evaluate the procedure's safety and effect on fracture healing. To date, there have been no intra-operative complications, and one non-device related adverse event. Of the nine patients who are at three-to-six months post-treatment, four have fractures that have united and four have experienced partial unions of the bone fracture. The lead investigator of this study which was sponsored by SpineSmith, LLC is Dr. Mark Lee of University of California, Davis, Medical Center.

"These outcomes demonstrate encouraging preliminary results with stem cell concentrates collected with our Res-Q System. CLI is a severe form of peripheral artery disease, with as many as 200,000 patients in the U.S. undergoing a limb amputation annually. Currently, there are more than 30 studies underway exploring stem cell therapy as an alternative treatment regimen for CLI patients. In addition, we are hopeful that stem cells will provide a new avenue for promoting the healing of serious bone fractures," said Matthew Plavan, Chief Executive Officer.

 

About ThermoGenesis Corp.

ThermoGenesis Corp. (www.thermogenesis.com) is a leader in developing and manufacturing automated blood processing systems and disposable products that enable the manufacture, preservation and delivery of cell and tissue therapy products. These include:

The BioArchive® System, an automated cryogenic device, used by cord blood stem cell banks in more than 30 countries for cryopreserving and archiving cord blood stem cell units for transplant. AXP® AutoXpress® Platform (AXP), a proprietary family of automated devices that includes the AXP and the MXP® MarrowXpress® and companion sterile blood processing disposables for harvesting stem cells in closed systems. The AXP device is used for the processing of cord blood. The MXP is used for the preparation of cell concentrates, including stem cells, from bone marrow aspirates in the laboratory setting. The Res-Q® 60 BMC/PRP (Res-Q), a point-of-care system designed for the preparation of cell concentrates, including stem cells, from bone marrow aspirates and whole blood for platelet rich plasma (PRP). The CryoSeal® FS System, an automated device and companion sterile blood processing disposable, used to prepare fibrin sealants from plasma in about an hour. The CryoSeal FS System is approved in the U.S. for liver resection surgeries. The CryoSeal FS System has received the CE-Mark which allows sales of the product throughout the European community.

This press release contains forward-looking statements.  These statements involve risks and uncertainties that could cause actual outcomes to differ materially from those contemplated by the forward-looking statements. Several factors including timing of FDA and foreign regulatory approvals, changes in customer forecasts, our failure to meet customers' purchase order and quality requirements, supply shortages, production delays, changes in the markets for customers' products, introduction timing and acceptance of our new products scheduled for fiscal year 2012, and introduction of competitive products and other factors beyond our control could result in a materially different revenue outcome and/or in our failure to achieve the revenue levels we expect for fiscal 2012.  A more complete description of these and other risks that could cause actual events to differ from the outcomes predicted by our forward-looking statements is set forth under the caption "Risk Factors" in our annual report on Form 10-K and other reports we file with the Securities and Exchange Commission from time to time, and you should consider each of those factors when evaluating the forward-looking statements.

 

 

ThermoGenesis Corp.
Web site: http://www.thermogenesis.com
Contact: Investor Relations
+1-916-858-5107, or
ir@thermogenesis.com

 

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ThermoGenesis Provides Update on Res-Q® Clinical Evaluations at Leading Stem Cell Therapy Conference

Experimental Neurology Journal: BrainStorm's NurOwn™ Stem Cell Technology Shows Promise for Treating Huntington's …

NEW YORK & PETACH TIKVAH, Israel--(BUSINESS WIRE)-- BrainStorm Cell Therapeutics Inc. (OTCBB: BCLI.OB - News), a leading developer of adult stem cell technologies and therapeutics, announced today that the prestigious Experimental Neurology Journal, published an article indicating that preclinical studies using cells that underwent treatment with Brainstorm’s NurOwn™ technology show promise in an animal model of Huntington’s disease. The article was published by leading scientists including Professor Melamed and Professor Offen of the Tel Aviv University.

In these studies, bone marrow derived mesenchymal stem cells secreting neurotrophic factors (MSC-NTF), from patients with Huntington’s disease, were transplanted into the animal model of this disease and showed therapeutic improvement.

“The findings from this study demonstrate that stem cells derived from patients with a neurodegenerative disease, which are processed using BrainStorm’s NurOwn™ technology, may alleviate neurotoxic signs, in a similar way to cells derived from healthy donors. This is an important development for the company, as it confirms that autologous transplantation may be beneficial for such additional therapeutic indications,” said Dr. Adrian Harel, BrainStorm’s CEO.

"These findings provide support once again that BrainStorm’s MSC-NTF secreting cells have the potential to become a platform that in the future will provide treatment for various neuro-degenerative diseases," says Chaim Lebovits, President of BrainStorm. "This study follows previously published pre-clinical studies that demonstrated improvement in animal models of neurodegenerative diseases such as Parkinson’s, Multiple Sclerosis (MS) and neural damage such as optic nerve transection and sciatic nerve injury. Therefore, BrainStorm will consider focusing on a new indication in the near future, in addition to the ongoing Clinical Trials in ALS.”

BrainStrom is currently conducting a Phase I/II Human Clinical Trial for Amyotrophic Lateral Sclerosis (ALS) also known as Lou Gehrig’s disease at the Hadassah Medical center. Initial results from the clinical trial (which is designed mainly to test the safety of the treatment), that were announced last week, have shown that the Brainstorm’s NurOwn™ therapy is safe and does not show any significant treatment-related adverse events and have also shown certain signs of beneficial clinical effects.

To read the Article entitled ‘Mesenchymal stem cells induced to secrete neurotrophic factors attenuate quinolinic acid toxicity: A potential therapy for Huntington's disease’ by Sadan et al. please go to:

http://www.sciencedirect.com/science/article/pii/S0014488612000295

About BrainStorm Cell Therapeutics, Inc.

BrainStorm Cell Therapeutics Inc. is a biotech company developing adult stem cell therapeutic products, derived from autologous (self) bone marrow cells, for the treatment of neurodegenerative diseases. The company, through its wholly owned subsidiary Brainstorm Cell Therapeutics Ltd., holds rights to develop and commercialize the technology through an exclusive, worldwide licensing agreement with Ramot at Tel Aviv University Ltd., the technology transfer company of Tel-Aviv University. The technology is currently in a Phase I/II clinical trials for ALS in Israel.

Safe Harbor Statement

Statements in this announcement other than historical data and information constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements, including, inter alia, regarding safety and efficacy in its human clinical trials and thereafter; the Company's ability to progress any product candidates in pre-clinical or clinical trials; the scope, rate and progress of its pre-clinical trials and other research and development activities; the scope, rate and progress of clinical trials we commence; clinical trial results; safety and efficacy of the product even if the data from pre-clinical or clinical trials is positive; uncertainties relating to clinical trials; risks relating to the commercialization, if any, of our proposed product candidates; dependence on the efforts of third parties; failure by us to secure and maintain relationships with collaborators; dependence on intellectual property; competition for clinical resources and patient enrollment from drug candidates in development by other companies with greater resources and visibility, and risks that we may lack the financial resources and access to capital to fund our operations. The potential risks and uncertainties include risks associated with BrainStorm's limited operating history, history of losses; minimal working capital, dependence on its license to Ramot's technology; ability to adequately protect its technology; dependence on key executives and on its scientific consultants; ability to obtain required regulatory approvals; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at http://www.sec.gov. The Company does not undertake any obligation to update forward-looking statements made by us.

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Experimental Neurology Journal: BrainStorm's NurOwn™ Stem Cell Technology Shows Promise for Treating Huntington's ...

Pro/Am Dancer is "Dancing with the Stars" Again After Stem Cell Therapy in Panama

Pro/Am ballroom dancer and orthodontist, Dr. Janet Vaughan, is once again slated to compete on the professional dance circuit with her current professional partner, Mr. Eddie Stutts (Professional 10-Dance World Champion) following a successful stem cell procedure on her knee in Panama.

Corpus Christi, TX (PRWEB) February 01, 2012

Pro/Am ballroom dancer and orthodontist, Dr. Janet Vaughan, is once again slated to compete on the professional dance circuit with her current professional partner, Mr. Eddie Stutts (Professional 10-Dance World Champion) following a successful stem cell procedure on her knee in Panama.

From 2007-2009, Dr. Vaughan partnered with World Champion Tony Dovolani and competed extensively in the U.S., winning a National Reserve Pro/Am Rhythm title. Tony Dovolani is best known for his appearances on ABC's hit reality series, "Dancing with the Stars", and has teamed up with Chynna Phillips, Wendy Williams, Audrina Partridge, Kate Gosselin, Kathy Ireland, Susan Lucci, Jane Seymour and other celebrities on the show.

Dr. Vaughan and Mr. Stutts are slated to compete in the Heritage Classic Dancesport Championships in Asheville, North Carolina next month. This will be the first time Dr. Vaughan has been able to compete since 2010 when she sustained a dancing related knee injury.

Dr. Vaughan also suffered from chronic neck pain resulting from injuries sustained in a car crash twenty years ago. Her neck injury culminated in a natural fusion of the c5-c6 vertebrae, scoliosis and extreme pain when her neck slipped out of alignment.

In an attempt to repair her knee and get her dancing career back on track, Dr. Vaughan decided to undergo stem cell therapy at the Stem Cell Institute in Panama City, Panama. "I was basically removed from competitive dance work because I could not rise or squat without extreme pain. I had also resigned myself to enduring chronic neck pain from my past accident and painful hand joints due to generalized arthritis," said Dr. Vaughan.

Dr. Vaughan 's knee was treated with stem cells that were harvested from her own adipose (fat) tissue.

The fat tissue sample is collected via mini-liposuction, which is performed by a certified plastic surgeon under light, general anesthesia. Mesenchymal stem cells and T regulatory cells reside within this tissue.

Adipose-derived cells are then separated from the fat at Medistem Panama’s state-of-the-art laboratory at the prestigious City of Knowledge. This entire process is subjected to stringent quality control. Before they can be administered back into the patient, these adipose-derived stem cells are tested for quality, bacterial contamination (aerobic and anaerobic) and endotoxin.

All patients treated with adipose stem cells at the Stem Cell Institute wait about one week before the stem cells can be re-implanted to minimize the probability of the cells migrating back to the liposuction injury site. This essential procedural step separates treatment in Panama from "same-day" protocols offered elsewhere.

The adipose-derived stem cells are administered by a highly-qualified physician into the affected joint(s) (intra-articular injection) and intravenously (IV).

"It's taken about 6 months but I am amazed at the results I've gotten with my knee. Even my neck is better. I used to spend almost $1,000 per month on a neuromuscular massage therapist but I haven't needed any neuromuscular massages for the past 6 months. I wasn't counting on that. Even my doctors say that the dense scar tissue in my neck has changed in texture from grizzly to smooth, supple tissue," exclaimed Dr. Vaughan.

She continued, "I just danced 6 hours in Houston preparing for the upcoming competition in Asheville and my knee isn't even sore."

Dr. Vaughan is planning to return to Panama for a follow-up treatment this summer.

About the Stem Cell Institute

Founded in 2006 on the principles of providing unbiased, scientifically-sound treatment options, the Stem Cell Institute has matured into the world’s leading adult stem cell therapy and research center. In close collaboration with universities and physicians world-wide, the institute’s doctors treat carefully selected patients with spinal cord injury, osteoarthritis, heart disease, multiple sclerosis, rheumatoid arthritis, and other autoimmune diseases. Doctors at The Stem Cell Institute have treated over 1000 patients to-date.

About Medistem Panama Inc.

Medistem performs all stem cell processing for the Stem Cell Institute. It operates an 8000 sq. ft. cGMP and cGMP compliant laboratory that features 3 class 10000 clean rooms, 8 class 100 laminar flow hoods, and 12 class 100 incubators.

For more information on stem cell therapy:

Stem Cell Institute Website: http://www.cellmedicine.com

Stem Cell Institute

Via Israel & Calle 66

Pacifica Plaza Office #2A

San Francisco, Panama

Republic of Panama

Phone: +1 800 980-STEM (7836) (USA Toll-free) +1 954 636-3390 (from outside USA)

Fax:    +1 866 775-3951 (USA Toll-free)    +1 775 887-1194 (from outside USA)

###

Jay Lenner
jdlenner@cellmedicine.com
1-800-980-7836
Email Information

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Pro/Am Dancer is "Dancing with the Stars" Again After Stem Cell Therapy in Panama

Stem Cell Therapy Shows Promise for Stroke, Studies Say

WEDNESDAY, Feb. 1 (HealthDay News) -- Treating stroke patients with stem cells taken from their own bone marrow appears to safely help them regain some of their lost abilities, two small new studies suggest.

Indian researchers observed mixed results in the extent of stroke patients' improvements, with one study showing marked gains in daily activities, such as feeding, dressing and movement, and the other study noting these improvements to be statistically insignificant. But patients seemed to safely tolerate the treatments in both experiments with no ill effects, study authors said.

"The results are encouraging to know but we need a larger, randomized study for more definitive conclusions," said Dr. Rohit Bhatia, a professor of neurology at the All India Institute of Medical Sciences in New Delhi, and author of one of the studies. "Many questions -- like timing of transplantation, type of cells, mode of transplantation, dosage [and] long-term safety -- need answers before it can be taken from bench to bedside."

The studies are scheduled to be presented Wednesday and Thursday at the American Stroke Association's annual meeting in New Orleans.

Stem cells -- unspecialized cells from bone marrow, umbilical cord blood or human embryos that can change into cells with specific functions -- have been explored as potential therapies for a host of diseases and conditions, including cancer and strokes.

In one of the current studies, 120 moderately affected stroke patients ranging from 18 to 75 years old were split into two groups, with half infused intravenously with stem cells harvested from their hip bones and half serving as controls. About 73 percent of the stem cell group achieved "assisted independence" after six months, compared with 61 percent of the control group, but the difference wasn't considered statistically significant.

In the other study, presented by Bhatia, 40 patients whose stroke occurred between three and 12 months prior were also split into two groups, with half receiving stem cells, which were dissolved in saline and infused over several hours. When compared to controls, stroke patients receiving stem cell therapy showed statistically significant improvements in feeding, dressing and mobility, according to the study. On functional MRI scans, the stem cell recipients also demonstrated an increase in brain activity in regions that control movement planning and motor function.

Neither study yielded adverse effects on patients, which could include tumor development.

But Dr. Matthew Fink, chief of the division of stroke and critical care neurology at New York-Presbyterian Hospital/Weill Cornell Medical Center, said that the therapy's safety is the only thing the two studies seemed to demonstrate.

"The thing to keep in mind is that these are really phase one trials," said Fink, also a professor of neurology at Weill Cornell Medical College. "I'm concerned that people get the idea that now stem cell treatment is available for stroke, and that's not the case."

Fink noted that the cells taken from study participants' hip bones can only be characterized as "bone marrow aspirates" since the authors didn't prove that actual stem cells were extracted.

"They haven't really analyzed if they're stem cells and what they turn into when they go into circulation," he added. "The best way to look at this is, it's very preliminary . . . when patients come to me to talk about it, I'm going to tell them it's years away before we know if this is going to work."

Studies presented at scientific conferences should be considered preliminary until published in a peer-reviewed medical journal.

More information

The U.S. National Institutes of Health has more information on stem cells.

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Stem Cell Therapy Shows Promise for Stroke, Studies Say

Stem Cell Treatment Offered At Oceanside Clinic Despite Controversy In Colorado

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Stem Cell Treatment Offered At Oceanside Clinic Despite Controversy In Colorado

'Personalized medicine' gets $67.5M research boost

The federal government is pledging up to $67.5 million for research into "personalized medicine," which tailors treatment to a patient's genetics and environment.

The funds will flow through Genome Canada, the Cancer Stem Cell Consortium and the Canadian Institutes of Health Research, the federal government's health research agency.

Federal Health Minister Leona Aglukkaq and Minister of State for Science Gary Goodyear made the announcement at the University of Ottawa's health campus Tuesday.

Personalized medicine takes into account a patient's genetics, environment and the course of the disease when deciding on treatment.

It can save on treatment costs and potentially decrease suffering if patients are treated more effectively and efficiently.

Researchers can get four years of funding for their projects, but they must have matching funding from another source, such as a provincial government or from the academic or private sectors.

The government says research could potentially address a wide scope of diseases and conditions, such as infectious diseases, cancer, mental health, skin diseases and rare diseases.

Additional research will look at the comparative effectiveness of treatment options as well as the ethical, environmental, economic, legal and social implications of integrating personalized medicine into the health-care system.

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'Personalized medicine' gets $67.5M research boost

BioRestorative Therapies Signs License Agreement for Stem Cell Disc/Spine Procedure

JUPITER, Fla., Jan. 31, 2012 /PRNewswire/ -- BioRestorative Therapies, Inc. (OTCQB: BRTX) ("BRT") today announced that it has entered into a License Agreement with Regenerative Sciences, LLC ("RS") with respect to certain stem cell-related technology and clinical treatment procedures developed by RS. The treatment is an advanced stem cell injection procedure that may offer relief from lower back pain, buttock and leg pain, or numbness and tingling in the legs or feet as a result of bulging and herniated discs.

To date, over 40 procedures have been performed on patients. It is a minimally invasive out-patient procedure, and objective MRI data and patient outcomes for this novel injection procedure show positive results with limited patient downtime. BRT intends to utilize the existing treatment and outcome data, as well as further research, to prepare for clinical trials in the United States.

Pursuant to the agreement, BRT will obtain an exclusive license to utilize or sub-license a certain medical device for the administration of specific cells and/or cell products to the precise locations within the damaged disc and/or spine (and other parts of the body, if applicable) and an exclusive license to utilize or sublicense a certain method for culturing cells for use in repairing damaged areas. The agreement contemplates a closing of the license grant in March 2012, subject to the fulfillment of certain conditions. 

Mark Weinreb, Chairman and CEO of BRT, said, "This possible alternative to back surgery represents a large market for BRT once it begins offering the procedure to patients who might be facing spinal fusions or back surgery (which often times is unsuccessful). By delivering a particular cell population using a proprietary medical device that inserts a specialized needle into the disc and injects cells for repair and re-population, BRT hopes to revolutionize how degenerative disc disease will be treated." 

About BioRestorative Therapies, Inc.
BioRestorative Therapies, Inc.'s goal is to become a medical center of excellence using cell and tissue protocols, primarily involving a patient's own (autologous) adult stem cells (non-embryonic), allowing patients to undergo cellular-based treatments. In June 2011, the Company launched a technology that involves the use of a brown fat cell-based therapeutic/aesthetic program, known as the ThermoStem™ Program.  The ThermoStem™ Program will focus on treatments for obesity, weight loss, diabetes, hypertension, other metabolic disorders and cardiac deficiencies and will involve the study of stem cells, several genes, proteins and/or mechanisms that are related to these diseases and disorders.  As more and more cellular therapies become standard of care, the Company believes its strength will be its focus on the unity of medical and scientific explanations for clinical procedures and outcomes for future personal medical applications.  The Company also plans to offer and sell facial creams and products under the Stem Pearls™ brand.

This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events or results to differ materially from those projected in the forward-looking statements as a result of various factors and other risks, including those set forth in the Company's Form 10, as amended, filed with the Securities and Exchange Commission. You should consider these factors in evaluating the forward-looking statements included herein, and not place undue reliance on such statements. The forward-looking statements in this release are made as of the date hereof and the Company undertakes no obligation to update such statements.

CONTACT:  Mark Weinreb, CEO, Tel: (561) 904-6070, Fax: (561) 429-5684

Originally posted here:
BioRestorative Therapies Signs License Agreement for Stem Cell Disc/Spine Procedure

Cancer patient receives stem cell-made windpipe, first in U.S.

The artificial windpipe implanted in Andemariam Teklesenbet Beyene, of Eritrea, in July 2011.

(Credit: University College London)

(CBS) In only the second operation of its kind, a Baltimore man has received an artificial windpipe made from stem cells to replace one destroyed by cancer.

PICTURES - First lab-grown windpipe saves cancer patient

Christopher Lyles, 30, had tracheal cancer that had progressed so far it was considered inoperable, the New York Times reported. In November, doctors made him a new windpipe - or trachea - made out of tiny plastic fibers seeded with stem cells from his own bone marrow.

Two months after his successful operation, Lyles arrived home in Md. last week.

Surgeon Paolo Macchiarini, a professor of regenerative surgery at Karolinska Institute in Stockholm, performed the surgery. He's also the doctor who performed the first surgery of this kind on a 31-year-old Eritrean man last July. Both surgeries were done in Stockholm.

"What we did is surgically remove his malignant tumor," Dr. Macchiarini told the Times. "Then we replaced the trachea with this tissue-engineered scaffold." The scaffold was placed in a container called a bioreactor and soaked in a solution that allows the cells to be fully absorbed. Once the windpipe was implanted, the cells continued to grow. "We're using the human body as a bioreactor to promote regeneration," Macchiarini said.

Is the operation fail-safe? "Time will tell what the longevity of these devices is, how long they last," Dr. Harald C. Ott, an instructor in surgery at Massachusetts General Hospital and Harvard Medical School, told the Boston Globe. Ott is unsure how the artificial material will integrate into the recipients' bodies, with both the biology of the body and the outside air that passes through the windpipe.

Researchers have used stem cell-seeding techniques to create other organs, including bladders and a urethra created at Wake Forest University.

Originally posted here:
Cancer patient receives stem cell-made windpipe, first in U.S.

Researchers turn skin cells into neural precusors, bypassing stem-cell stage

The multiple successes of the direct conversion method could refute the idea that pluripotency (a term that describes the ability of stem cells to become nearly any cell in the body) is necessary for a cell to transform from one cell type to another. Together, the results raise the possibility that embryonic stem cell research and another technique called "induced pluripotency" could be supplanted by a more direct way of generating specific types of cells for therapy or research.

This new study, which will be published online Jan. 30 in the Proceedings of the National Academy of Sciences, is a substantial advance over the previous paper in that it transforms the skin cells into neural precursor cells, as opposed to neurons. While neural precursor cells can differentiate into neurons, they can also become the two other main cell types in the nervous system: astrocytes and oligodendrocytes. In addition to their greater versatility, the newly derived neural precursor cells offer another advantage over neurons because they can be cultivated to large numbers in the laboratory — a feature critical for their long-term usefulness in transplantation or drug screening.

In the study, the switch from skin to neural precursor cells occurred with high efficiency over a period of about three weeks after the addition of just three transcription factors. (In the previous study, a different combination of three transcription factors was used to generate mature neurons.) The finding implies that it may one day be possible to generate a variety of neural-system cells for transplantation that would perfectly match a human patient.

"We are thrilled about the prospects for potential medical use of these cells," said Marius Wernig, MD, assistant professor of pathology and a member of Stanford's Institute for Stem Cell Biology and Regenerative Medicine. "We've shown the cells can integrate into a mouse brain and produce a missing protein important for the conduction of electrical signal by the neurons. This is important because the mouse model we used mimics that of a human genetic brain disease. However, more work needs to be done to generate similar cells from human skin cells and assess their safety and efficacy."

Wernig is the senior author of the research. Graduate student Ernesto Lujan is the first author.

While much research has been devoted to harnessing the pluripotency of embryonic stem cells, taking those cells from an embryo and then implanting them in a patient could prove difficult because they would not match genetically. An alternative technique involves a concept called induced pluripotency, first described in 2006. In this approach, transcription factors are added to specialized cells like those found in skin to first drive them back along the developmental timeline to an undifferentiated stem-cell-like state. These "iPS cells" are then grown under a variety of conditions to induce them to re-specialize into many different cell types.

Scientists had thought that it was necessary for a cell to first enter an induced pluripotent state or for researchers to start with an embryonic stem cell, which is pluripotent by nature, before it could go on to become a new cell type. However, research from Wernig's laboratory in early 2010 showed that it was possible to directly convert one "adult" cell type to another with the application of specialized transcription factors, a process known as transdifferentiation.

Wernig and his colleagues first converted skin cells from an adult mouse to functional neurons (which they termed induced neuronal, or iN, cells), and then replicated the feat with human cells. In 2011 they showed that they could also directly convert liver cells into iN cells.

"Dr. Wernig's demonstration that fibroblasts can be converted into functional nerve cells opens the door to consider new ways to regenerate damaged neurons using cells surrounding the area of injury," said pediatric cardiologist Deepak Srivastava, MD, who was not involved in these studies. "It also suggests that we may be able to transdifferentiate cells into other cell types." Srivastava is the director of cardiovascular research at the Gladstone Institutes at the University of California-San Francisco. In 2010, Srivastava transdifferentiated mouse heart fibroblasts into beating heart muscle cells.

"Direct conversion has a number of advantages," said Lujan. "It occurs with relatively high efficiency and it generates a fairly homogenous population of cells. In contrast, cells derived from iPS cells must be carefully screened to eliminate any remaining pluripotent cells or cells that can differentiate into different lineages." Pluripotent cells can cause cancers when transplanted into animals or humans.

The lab's previous success converting skin cells into neurons spurred Wernig and Lujan to see if they could also generate the more-versatile neural precursor cells, or NPCs. To do so, they infected embryonic mouse skin cells — a commonly used laboratory cell line — with a virus encoding 11 transcription factors known to be expressed at high levels in NPCs. A little more than three weeks later, they saw that about 10 percent of the cells had begun to look and act like NPCs.

Repeated experiments allowed them to winnow the original panel of 11 transcription factors to just three: Brn2, Sox2 and FoxG1. (In contrast, the conversion of skin cells directly to functional neurons requires the transcription factors Brn2, Ascl1 and Myt1l.) Skin cells expressing these three transcription factors became neural precursor cells that were able to differentiate into not just neurons and astrocytes, but also oligodendrocytes, which make the myelin that insulates nerve fibers and allows them to transmit signals. The scientists dubbed the newly converted population "induced neural precursor cells," or iNPCs.

In addition to confirming that the astrocytes, neurons and oligodendrocytes were expressing the appropriate genes and that they resembled their naturally derived peers in both shape and function when grown in the laboratory, the researchers wanted to know how the iNPCs would react when transplanted into an animal. They injected them into the brains of newborn laboratory mice bred to lack the ability to myelinate neurons. After 10 weeks, Lujan found that the cells had differentiated into oligodendroytes and had begun to coat the animals' neurons with myelin.

"Not only do these cells appear functional in the laboratory, they also seem to be able to integrate appropriately in an in vivo animal model," said Lujan.

The scientists are now working to replicate the work with skin cells from adult mice and humans, but Lujan emphasized that much more research is needed before any human transplantation experiments could be conducted. In the meantime, however, the ability to quickly and efficiently generate neural precursor cells that can be grown in the laboratory to mass quantities and maintained over time will be valuable in disease and drug-targeting studies.

"In addition to direct therapeutic application, these cells may be very useful to study human diseases in a laboratory dish or even following transplantation into a developing rodent brain," said Wernig.

Provided by Stanford University Medical Center (news : web)

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Researchers turn skin cells into neural precusors, bypassing stem-cell stage