Doctors Use Adult (Not Embryonic) Stem Cells To Grow And Implant Petri-Dish Retina

The clones are coming! The clones are coming! (Maybe.) Doctors have grown a retina in a petri dish using stem cells from a 70-year-old patients skin and successfully transplanted the retina to her eye at Japan's Riken Center for Developmental Biology.

This marks the first time a transplanted organ was grown from skin cells from the recipient and not an embryo, The Globe and Mail reports. Until now, scientists have been mired in a debate regarding the use of embryonic stem cells to create transplant tissue. Using a patients own adult stem cells avoids that controversy and also reduces the chance the patient could reject the transplant.

Stem cells hold the promise of curing many diseases, including macular degeneration and Parkinsons.

However, there are risks associated with using adult stem cells. Scientists must turn regular adult cells into dividing cells, and there is concern that cells could turn cancerous after transplant. You only need one stem cell left in the graft that could lead to cancer, Dr. Janet Rossant told the The Globe and Mail. Rossant is chief of research at Torontos Hospital for Sick Children and past president of the International Society for Stem Cell Research.

The Riken Center for Developmental Biology has also been in the news lately because its deputy director committed suicide following accusations of scientific misconduct and the retraction of two papers (unrelated to this stem-cell procedure) that were published in the journal Nature.

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Doctors Use Adult (Not Embryonic) Stem Cells To Grow And Implant Petri-Dish Retina

Dana-Farber and other researchers find that silencing the speech gene FOXP2 causes breast cancer cells to metastasize

NCI Cancer Center News

A research team led by investigators at Beth Israel Deaconess Medical Center has identified an unexpected link between a transcription factor known to regulate speech and language development and metastatic colonization of breast cancer. Currently described online in Cell Stem Cell, the new findings demonstrate that, when silenced, the FOXP2 transcription factor, otherwise known as the speech gene, endows breast cancer cells with a number of malignant traits and properties that enable them to survive and thrive.

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Among the research institutions NCI funds across the United States, it currently designates 68 as Cancer Centers. Largely based in research universities, these facilities are home to many of the NCI-supported scientists who conduct a wide range of intense, laboratory research into cancers origins and development. The Cancer Centers Program also focuses on trans-disciplinary research, including population science and clinical research. The centers research results are often at the forefront of studies in the cancer field.

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Dana-Farber and other researchers find that silencing the speech gene FOXP2 causes breast cancer cells to metastasize

Silencing the Speech Gene FOXP2 Causes Breast Cancer Cells to Metastasize

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Newswise BOSTON It is an intricate network of activity that enables breast cancer cells to move from the primary breast tumor and set up new growths in other parts of the body, a process known as metastasis.

Now a research team led by investigators at Beth Israel Deaconess Medical Center (BIDMC) has identified an unexpected link between a transcription factor known to regulate speech and language development and metastatic colonization of breast cancer.

Currently described online in Cell Stem Cell, the new findings demonstrate that, when silenced, the FOXP2 transcription factor, otherwise known as the speech gene, endows breast cancer cells with a number of malignant traits and properties that enable them to survive and thrive.

We have identified a previously undescribed function for the transcription factor FOXP2 in breast cancer, explains senior author Antoine Karnoub, PhD, an investigator in the Department of Pathology at BIDMC and Assistant Professor of Pathology at Harvard Medical School. We have found that depressed FOXP2 [a member of the forkhead family of transcriptional regulators] and elevated levels of its upstream inhibitor microRNA 199a are prominent features of clinically advanced breast cancers that associate with poor patient survival.

Karnoubs lab investigates the roles that mesenchymal stem cells (MSCs) play in the development and metastasis of breast cancer. MSCs are adult progenitor cells that function as the bodys early responders, poised to take action to help repair damaged tissues, jumping from their niches in the bone, for example, into the blood, migrating to areas of inflammation, and orchestrating the bodys reactions during wound healing. Previous work by Karnoub revealed that MSCs respond to breast tumors akin to the way they react to a wound or infection and that these cells participate in the formation of the breast tumor stroma, the supporting network of cells and their secretions that exist in the microenvironment of cancer cells.

We think that by direct actions on the cancer cells and by manipulating other cells in the microenvironment, MSCsend up providing cancer cells with better abilities to survive and a safe haven in which to thrive, says Karnoub. Despite expanding knowledge of the role of MSCs to breast malignancy, the underlying molecular responses of breast cancer cells to MSC influences has not been fully delineated. In this new paper, the investigators set out to specifically identify the role that microRNAs were playing in the process.

miRNAs are short noncoding RNAs that play critical functions in cancer pathogenesis,. An expanding body of evidence has documented miRNA deregulation in multiple aspects of tumor development, including invasion and metastasis, says Karnoub. The induction by MSCs of one such miRNA, miR199a, facilitated the acquisition of malignant properties by the cancer cells, including cancer stem cell and metastatic traits. (Cancer stem cells are thought to be the most virulent cells that lie within the core of most tumors, and are believed to be responsible for the resurgence of tumors following chemotherapy treatment.)

After we found that miRNA-199a instigated in the cancer cells by MSCs was indeed promoting these cancer stem cells phenotypes and was facilitating cancer metastasis, we probed the mechanistic details of miR-199as actions, explains Karnoub. miRNAs function predominantly by suppressing target mRNA expression, and we analyzed an overwhelming majority of the published targets that have been associated with these miRNAs, but none was repressed in our systems. We then made a screen and serendipitously fished out a gene called FOXP2. At that time, he adds, basically nothing was known about this protein in relation to breast cancer.

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Silencing the Speech Gene FOXP2 Causes Breast Cancer Cells to Metastasize

NYSCF Research Institute announces largest-ever stem cell repository

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The New York Stem Cell Foundation (NYSCF) Research Institute, through the launch of its repository in 2015, will provide for the first time the largest-ever number of stem cell lines available to the scientific research community. Initially, over 600 induced pluripotent stem (iPS) cell lines and 1,000 cultured fibroblasts from over 1,000 unique human subjects will be made available, with an increasing number available in the first year. To collect these samples, NYSCF set up a rigorous human subjects system that protects patients and allows for the safe and anonymous collection of samples from people interested in participating in research.

A pilot of over 200 of NYSCF's iPS cell lines is already searchable on an online database. The pilot includes panels of iPS cell lines generated from donors affected by specific diseases such as type 1 diabetes, Parkinson's disease, and multiple sclerosis, as well as a diversity panel of presumed healthy donors from a wide range of genetic backgrounds representing the United States Census. These panels, curated to provide ideal initial cohorts for studying each area, include subjects ranging in age of disease onset, and are gender matched. Other panels that will be available in 2015 include Alzheimer's disease, schizophrenia, Juvenile Batten disease, and Charcot-Marie-Tooth disease.

"NYSCF's mission is to develop new treatments for patients. Building the necessary infrastructure and making resources available to scientists around the world to further everyone's research are critical steps in accomplishing this goal," said Susan L. Solomon, CEO of The New York Stem Cell Foundation.

NYSCF has developed the technology needed to create a large collection of stem cell lines representing the world's population. This platform, known as the NYSCF Global Stem Cell ArrayTM, is an automated robotic system for stem cell production and is capable of generating 200 iPS cell lines a month from patients with various diseases and conditions and from all genetic backgrounds. The NYSCF Global Stem Cell ArrayTM is also used for stem cell differentiation and drug screening.

Currently available in the online database that was developed in collaboration with eagle-i Network, of the Harvard Catalyst, is a pilot set of approximately 200 iPS cell lines and related information about the patients. This open source, open access resource discovery platform makes the cell lines and related information available to the public on a user-friendly, web-based, searchable system. This is one example of NYSCF's efforts to reduce duplicative research and enable even broader collaborative research efforts via data sharing and analysis. NYSCF continues to play a key role in connecting the dots between patients, scientists, funders, and outside researchers that all need access to biological samples.

"The NYSCF repository will be a critical complement to other existing efforts which are limited in their ability to distribute on a global scale. I believe that this NYSCF effort wholly supported by philanthropy will help accelerate the use of iPS cell based technology," said Dr. Mahendra Rao, NYSCF Vice President of Regenerative Medicine.

To develop these resources, NYSCF has partnered with over 50 disease foundations, academic institutions, pharmaceutical companies, and government entities, including the Parkinson's Progression Markers Initiative (PPMI), PersonalGenomes.org, the Beyond Batten Disease Foundation, among several others. NYSCF also participates in and drives a number of large-scale multi stakeholder initiatives including government and international efforts. One such example is the Cure Alzheimer's Fund Stem Cell Consortium, a group consisting of six institutions, including NYSCF, directly investigating, for the first time, brain cells in petri dishes from individual patients who have the common sporadic form of Alzheimer's disease.

"We are entering this next important phase of using stem cells to understand disease and discover new drugs. Having collaborated with NYSCF extensively over the last five years on the automation of stem cell production and differentiation, it's really an exciting moment to see these new technologies that NYSCF has developed now being made available to the entire academic and commercial research communities," said Dr. Kevin Eggan, Professor of Stem Cell and Regenerative Biology at Harvard University and Principal Investigator of the Harvard Stem Cell Institute.

NYSCF's unique technological resources have resulted in partnerships with companies to develop both stem cell lines and also collaborative research programs. Over the past year, NYSCF has established collaborations with four pharmaceutical companies to accelerate the translation of basic scientific discoveries into the clinic. Federal and state governments are also working with NYSCF to further stem cell research in the pursuit of cures. In 2013, NYSCF partnered with the National Institutes of Health (NIH) Undiagnosed Disease Program (UDP) to generate stem cell lines from 100 patients in the UDP and also collaborate with UDP researchers to better understand and potentially treat select rare diseases.

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NYSCF Research Institute announces largest-ever stem cell repository

UC San Diego Health System announces human testing of stem cell therapies

SAN DIEGO (CNS) - UC San Diego Health System announced Monday that human testing of injected neural stem cell therapies are underway at its Sanford Stem Cell Clinical Center.

Researchers are conducting three different trials -- one on a 26-year-old woman paralyzed after a traffic crash, and others on diabetes and leukemia patients.

"What we are seeing after years of work is the rubber hitting the road," said Lawrence Goldstein, director of the UC San Diego Stem Cell program and Sanford Stem Cell Clinical Center.

"These are three very ambitious and innovative trials," he said. "Each followed a different development path -- each addresses a very different disease or condition. It speaks to the maturation of stem cell science that we've gotten to the point of testing these very real medical applications in people."

The first tests are being made with low doses in order to ensure the safety of the patients, Goldstein said.

Working with Maryland-based Neuralstem Inc., neural stem cells were injected into the site of the paralyzed woman's spinal cord injury on Sept. 30, and she is recovering at home without complications or adverse effects, said Dr. Joseph Ciacci, a neurosurgeon at UC San Diego Health System. Her name was not released.

The researchers hope that the transplanted cells will develop into neurons that bridge the gap created by the injury, replace severed or lost nerve connections and restore at least some motor and sensory function. According to UCSD, testing in laboratory rats with spinal cord injuries were promising.

A two-year trial on about 40 Type 1 diabetes patients will involve implanting cells under the skin that were derived from embryonic stem cells, with the hope they will safely mature into pancreatic beta and other cells able to produce a continuous supply of needed insulin and other substances, according to the researchers. The first procedure is expected to take place sometime this month, according to UCSD.

Type 1 diabetes, which usually onsets during childhood and has no cure, causes the pancreas to produce little or no insulin. Patients have to inject insulin daily and rigorously manage their diet and lifestyle.

The third trial will involve a potential drug to fight chronic lymphocytic leukemia, the most common form of blood cancer in adults. Patients in the test will receive the drug via an intravenous infusion every 14 days at the UCSD Moores Cancer Center.

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UC San Diego Health System announces human testing of stem cell therapies

UCSD Stem Cell program begins human testing

SAN DIEGO (CNS) - UC San Diego Health System announced Monday that human testing of injected neural stem cell therapies are underway at its Sanford Stem Cell Clinical Center.

Researchers are conducting three different trials -- one on a 26-year-old woman paralyzed after a traffic crash, and others on diabetes and leukemia patients.

"What we are seeing after years of work is the rubber hitting the road," said Lawrence Goldstein, director of the UC San Diego Stem Cell program and Sanford Stem Cell Clinical Center.

"These are three very ambitious and innovative trials," he said. "Each followed a different development path -- each addresses a very different disease or condition. It speaks to the maturation of stem cell science that we've gotten to the point of testing these very real medical applications in people."

The first tests are being made with low doses in order to ensure the safety of the patients, Goldstein said.

Working with Maryland-based Neuralstem Inc., neural stem cells were injected into the site of the paralyzed woman's spinal cord injury on Sept. 30, and she is recovering at home without complications or adverse effects, said Dr. Joseph Ciacci, a neurosurgeon at UC San Diego Health System. Her name was not released.

The researchers hope that the transplanted cells will develop into neurons that bridge the gap created by the injury, replace severed or lost nerve connections and restore at least some motor and sensory function. According to UCSD, testing in laboratory rats with spinal cord injuries were promising.

A two-year trial on about 40 Type 1 diabetes patients will involve implanting cells under the skin that were derived from embryonic stem cells, with the hope they will safely mature into pancreatic beta and other cells able to produce a continuous supply of needed insulin and other substances, according to the researchers. The first procedure is expected to take place sometime this month, according to UCSD.

Type 1 diabetes, which usually onsets during childhood and has no cure, causes the pancreas to produce little or no insulin. Patients have to inject insulin daily and rigorously manage their diet and lifestyle.

The third trial will involve a potential drug to fight chronic lymphocytic leukemia, the most common form of blood cancer in adults. Patients in the test will receive the drug via an intravenous infusion every 14 days at the UCSD Moores Cancer Center.

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UCSD Stem Cell program begins human testing

Scientists Grow, Implant Human Intestinal Tissue in Mice

SUNDAY, Oct. 19, 2014 (HealthDay News) -- New stem cell-based research could improve understanding of intestinal diseases and eventually lead to new treatments, a new study suggests.

Scientists used stem cells to grow "organoids" of functioning human intestinal tissue in a lab dish. They then transplanted the organoids into mice, creating a new model for studying intestinal disorders, according to the researchers.

"This provides a new way to study the many diseases and conditions that can cause intestinal failure, from genetic disorders appearing at birth to conditions that strike later in life, such as cancer and Crohn's disease," lead investigator Dr. Michael Helmrath, surgical director of the Intestinal Rehabilitation Program at the Cincinnati Children's Hospital Medical Center, said in a center news release.

"These studies also advance the longer-term goal of growing tissues that can replace damaged human intestine," he added.

Further research could eventually lead to the ability to create personalized human intestinal tissue to treat gastrointestinal diseases, according to the researchers.

"These studies support the concept that patient-specific cells can be used to grow intestine," Helmrath explained.

The research was published online Oct. 19 in the journal Nature Medicine.

The intestinal organoids were created using so-called pluripotent stem cells, which can become any type of tissue in the body. The scientists created these "blank" stem cells by reprogramming adult cells taken from skin and blood samples.

The stem cells were placed in lab dishes with a specific molecular mixture that prompted the cells to grow into intestinal organoids, which developed into fully mature, functioning human intestinal tissue after being transplanted into mice.

The mice were genetically engineered so that their immune systems would not reject the human tissue, the study authors noted.

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Scientists Grow, Implant Human Intestinal Tissue in Mice

Researchers in Berlin and Bath Identify Nave-Like Human Stem Cells

16.10.2014 - (idw) Max-Delbrck-Centrum fr Molekulare Medizin (MDC) Berlin-Buch

In their search for the earliest possible stage of development of human embryonic stem cells (hESCs) that still have the potential to develop into any types of body cells and tissue, researchers from the Max Delbrck Center for Molecular Medicine (MDC) Berlin-Buch, Germany, and the University of Bath, United Kingdom, have apparently been successful. Jichang Wang, Gangcai Xie, and Dr. Zsuzsanna Izsvk (MDC), together with Professor Laurence D. Hurst (University of Bath), report the discovery of a subtype of cells in culture dishes with hESCs and human induced pluripotent stem cells (hiPSCs) that resemble this very early, pluripotent or nave state (Nature, doi:10.1038/nature13804)*. They also discovered the mechanism that turns human ES cells into nave-like human stem cells. While this has potential implications for medicine and for understanding early human development, an evolutionary enigma still remains unsolved.

Human embryonic stem cells (hESCs) differ considerably from those of mice. Mouse nave cultures resemble the inner cell mass which gives rise to the embryo, while none of the cultured hESC lines do. Nave ESCs of mice are easy to maintain, but not human ESCs isolated from pre-implantation embryos. The hESC lines, researchers work with in their laboratories are considered to be less nave, and have limited differentiation potential. Researchers hypothesize that they have partially lost their pluripotency. Why this is so remains unclear.

What properties characterize human nave stem cells? Can they be identified and proliferated in the laboratory and retained in culture? Researchers in Europe, Asia and the USA are trying to find the answers to these questions in order to be able to use these cells for therapy in the future.

Evolution pointed the way It was evolution that showed the researchers in Bath and Berlin the way to the successful approach. They pinpointed one particular class of ancient viruses called HERVH (human endogenous retrovirus H). HERVH integrated into our DNA millions of years ago, and although it does not function as a virus any longer, it is not silent.

HERVH-derived sequences appear at a very early stage in human embryos, that is, HERVH is highly expressed at just the right time and place in human embryos where one would expect to see nave stem cells. This was also observed by Professor Kazutoshi Takahashi (Kyoto University, Kyoto, Japan), almost at the same time when Dr. Izsvk and Professor Hurst made their discovery.**

Dr. Izsvk and Professor Hurst succeeded in going one step further. They were able to identify the switch that regulates HERVH. In hESC cultures they identified a transcription factor called LBP9 as being central to the activity of HERVH in early embryos. Using a reporter system that made cells expressing HERVH via LBP9 glow green, the Berlin and Bath team found that they had purified human ESCs that showed all the hallmarks of nave mouse stem cells.

This transcription factor was not previously known to be important to human stem cells. However, unknown to them at the time, the same transcription factor was shown by Austin Smiths group (University of Cambridge, UK) to have a role in mouse nave cells***.

Our human nave-like cells look remarkably like the mouse ones, and are close to human inner cell mass (ICM), said Jichang Wang (PhD student, MDC), first author of the Nature publication. With our HERVH-based reporter system we can easily isolate nave-like human ESCs from any human ESC culture. These cells grow like the mouse nave stem cells and express many of the same genes such as NANOG, KLF4 and OCT4 that are associated with murine navet. When we knockdown LBP9 or HERVH, these cells no longer resemble nave-like human stem cells, he added.

To explore a potential role in stem cell-based therapeutics, the next task will be to keep these isolated human nave-like stem cells in culture and proliferate them. HERVH would also be particularly useful in identifying optimal conditions for long-term culturing. As HERVH inhibits differentiation, its expression should be transient, otherwise it might be detrimental to normal embryo development. What factors keep this delicate process in balance is yet to be determined.

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Researchers in Berlin and Bath Identify Nave-Like Human Stem Cells

Discovery of Repair Process After Heart Attack Suggests Potential for New Treatment Strategy

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Newswise In a study that could point the way toward a new strategy for treating patients after a heart attack, UCLA stem cell researchers led by associate professor of medicine (cardiology) and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research member Dr. Arjun Deb have discovered that some scar-forming cells in the heart, known as fibroblasts, have the ability to become endothelial cells (the cells that form blood vessels). The UCLA team also found that a drug could enhance this phenomenon and improve the repair process after a heart attack.

The findings are reported in the October 15, 2014 edition of the journal Nature.

It is well known that increasing the number of blood vessels in the injured heart following a heart attack improves its ability to heal, said Dr. Deb, the studys senior author. We know that scar tissue in the heart is associated with a poorer prognosis. Reversing or preventing scar tissue from forming has been one of the major challenges of cardiovascular medicine.

Heart disease remains a leading cause of death in the United States. Each year in this country, approximately 720,000 people experience a heart attack (roughly one every 30 seconds) and about 600,000 people die of heart disease.

A heart attack most commonly occurs when there is a sudden blockage of the flow of blood through a vessel in the heart. The portion of the heart muscle that fails to receive adequate blood dies and is replaced by non-functional scar tissue (a process known as fibrosis) reducing the ability of the heart to adequately pump blood. Once scar forms it is thought to persist throughout the lifetime of the individual. Scar-forming cells (fibroblasts) and blood vessel-forming cells (endothelial cells) exist in close proximity in the injured heart.

Several years ago, Dr. Deb and his colleagues were investigating the relationship between the fibroblasts and endothelial cells. Performing experiments in mice in which scar-forming cells in the heart were genetically labeled, the researchers unexpectedly discovered that many of the fibroblasts in the hearts injured region changed into endothelial cells and contributed directly to blood vessel formation, a phenomenon the research team coined mesenchymal-endothelial transition, or MEndoT.

The researchers identified a molecular mechanism regulating MEndoT and administering a small molecule to augment MEndoT led to less scarring and better healing of the heart. The researchers plan to test similar small molecules in other models to determine whether the strategy could potentially be translated for human benefit.

Our findings suggest the possibility of coaxing scar-forming cells in the heart to change their identity into blood vessel-forming cells, which could potentially be a useful approach for better heart repair, said Dr. Deb. There are remarkable similarities in the process of scarring in different organs after injury. Our hope is that this approach can be used to treat scar tissue in other organs as well.

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Discovery of Repair Process After Heart Attack Suggests Potential for New Treatment Strategy

Vision Quest: Stem Cells Treat Blinding Disease

Powerful stem cells injected into the eyes of 18 patients with diseases causing progressive blindness have proven safe and dramatically improved the vision of some of the patients, scientists report.

Three years of follow up show that vision improved measurably in seven of the patients, the team at Advanced Cell Technology report in the Lancet medical journal. In some cases, the improvement was dramatic.

For instance, we treated a 75-year-old horse rancher who lives in Kansas, said Dr. Robert Lanza, chief medical officer for the Massachusetts-based company. The rancher had poor vision 20/400 in one eye.

Once month after treatment his vision had improved 10 lines (20/40) and he can even ride his horses again. Other patients report similarly dramatic improvements in their lives, Lanza added. For instance, they can use their computers or read their watch. Little things like that which we all take for granted have made a huge difference in the quality of their life.

Not all the patients improved and one even got worse. But overall, Lanzas team reported, the patients vision improved by three lines on a standard vision chart.

"They can use their computers or read their watch. Little things like that which we all take for granted have made a huge difference in the quality of their life.

The researchers treated only one eye in each patient. There was no improvement in vision in the untreated eyes.

The patients had either Stargardts disease, a common type of macular degeneration, or dry macular degeneration, which is the leading cause of blindness in the developed world. There are no treatments for either condition, and patients gradually lose vision over the years until they are, often, blind.

Lanzas team used human embryonic stem cells, made using human embryos. They are powerful cells, each one capable of giving rise to all the cells and tissues in the body. The ACT team took one cell from embryos at the eight-cell stage to make batches of these cells.

They reprogrammed them to make immature retinal cells, which they injected into the eyes of the patients. The hope is that the immature cells would take up the places of the degenerated cells and restore vision.

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Vision Quest: Stem Cells Treat Blinding Disease