Researchers uncover mechanism blocking retina regeneration

A discovery opens the possibility of one day restoring loss of vision by activating the retina’s ability to regenerate

By Graciela Gutierrez

Researchers at Baylor College of Medicine, the Cardiovascular Research Institute and the Texas Heart Institutereveal in the journal Cell Reports that although the mammalian retina – a layer of specialized nerve cells that mediates vision and is located on the back of the eye– does not spontaneously regenerate, it has a regenerative capacity that is kept dormant by a cellular mechanism called the Hippo pathway. The discovery opens the possibility of activating the retina’s ability to restore lost vision by manipulating this pathway.

“Damage to the retina can lead to irreparable loss of vision in humans and other mammals because their retinas do not regenerate,” said lead author Dr. Ross A. Poché, assistant professor of molecular physiology and biophysics and member of the Dan L Duncan Comprehensive Cancer Center at Baylor. “However, other animals such as zebrafish can reverse blindness thanks to specialized cells in the retina called Müller glial cells. When the retina is damaged, Müller glial cells proliferate and differentiate into the lost retinal neurons, effectively replacing injured cells with fully functional ones.”

Although Müller glial cells in injured mammalian retina do not restore vision as their counterpart in zebrafish do, other researchers have shown that, when the mammalian retina is injured, a small subset of Müller glial cells takes the first steps needed to enter the proliferation cycle, such as acquiring molecular markers scientists expect to see in a proliferating cell.

“But this attempt to proliferate is transient; after acquiring some of the cell markers the cells shut off,” said Poché, who also is affiliated with the Intellectual and Developmental Disabilities Research Center and the Cullen Eye Institute, both at Baylor. “These observations suggested that the mechanism that drives cell repair in zebrafish also might be present in mammals, but it is actively suppressed. For years, the suppressing mechanism was unknown.”

Searching for the proposed suppressing mechanism, the Poché lab joined forces with the lab of co-corresponding author Dr. James Martin, professor of molecular physiology and biophysics, Vivian L. Smith Chair in Regenerative Medicine at Baylor College of Medicine and director of the Cardiomyocyte Renewal Lab at the Texas Heart Institute. The researchers focused their attention on the Hippo pathway, a network of molecular events that contributes to organ growth during development and to the regulation of heart tissue regeneration in response to myocardial infarction. The Martin lab previously showed that the Hippo pathway acts like a ‘break’ on cardiomyocyte proliferation by inhibiting the activity of another pathway called YAP.

In this study, the researchers first determined that the Hippo pathway is expressed in mammalian Müller glial cells. Then, they investigated whether altering the Hippo pathway in these cells would affect their ability to proliferate. Creating a malfunctioning Hippo pathway by eliminating two of its molecular steps resulted in modest cell proliferation. And when the researchers genetically engineered Müller glial cells to carry a version of YAP called YAP5SA that is impervious to the inhibitory influence of Hippo, the cells showed major proliferation and acquired a progenitor cell identity. Importantly, a small subset of these Müller glia-derived progenitor cells showed signs of spontaneous differentiation into new retinal neurons. 

“Up to this point researchers did not know what endogenous blocking mechanism prevented Müller cells from entering a regenerative state. The Hippo pathway is a new molecular entry point to that mechanism,” said Poché. “Our next step is to develop a strategy to guide proliferating Müller glial cells into differentiation pathways leading to retinal cells capable of restoring vision.”

Other contributors to this work include Elda M. Rueda, Benjamin M. Hall, Matthew C. Hill, Paul G. Swinton and Xuefei Tong. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, the Cardiovascular Research Institute and the Texas Heart Institute.

This work was supported by National Institutes of Health grants P30 AI036211, P30 CA125123, S10 RR024574, U543 HG006348, R01 EY024906, R01 DE023177, R01 HL127717, R01 HL118761, R01 HL130804 and F31 HL136065. Additional support was provided by the Vivian L. Smith Foundation, MacDonald Research Fund award 16RDM001 and the Bright Focus Foundation Macular Degeneration Research Grant  M2018022 .

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By |May 8th, 2019|Uncategorized|0 Comments

Proposed Legislation Would Regulate Stem Cell Therapy Clinic Claims

Source: KomoNews.com

(Olympia, Washington) — If proposed legislation wins approval in Olympia next week – many clinics promoting stem cell therapy will have to make it clear when the treatment they’re selling is not approved by the Food and Drug Administration.

Right now, the only proven stem cell therapies deal with blood regeneration- treatments such as bone marrow transplants, cord blood transplants and similar procedures that have been well documented to regenerate your blood forming abilities.

Stem cell researchers, medical experts and researchers at the FDA warn everything else is experimental.

Under ESHB 2356, the Stem Cell Therapy Bill being considered in Olympia, facilities offering stem cell treatments must notify you about therapies that are not approved by the FDA. They have to put it in writing and get your written consent.

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By |February 23rd, 2018|Uncategorized|0 Comments

A&M and Celltex partner on stem cell Alzheimer’s research

Source: Houston Chronicle

(Houston, Texas) — Texas A&M University Health Science Center is partnering with the Houston company that ran into trouble with federal regulators a year after facilitating the 2011 stem cell treatment of Gov. Rick Perry’s ailing back.

Celltex Therapeutics Corp. and A&M’s Institute for Regenerative Medicine Tuesday announced an intellectual property licensing deal involving research on a potential stem cell therapy for Alzheimer’s disease. A&M researchers say the therapy shows promise where drugs typically fail.

“In mice to whom we did terrible things to damage brain function, this therapy restored memory,” said Dr. Darwin Prockop, director of the A&M Institute for Regenerative Medicine and the leader of the laboratory team working on the project. “Through this deal, we hope to start bringing it to human patients within three years.”

Celltex will pay Texas A&M $2.4 million to acquire the technology and ultimately bring it to market.

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By |February 7th, 2018|Uncategorized|0 Comments

First Cow Embryonic Stem Cells Derived

Source: Science Magazine

(East Lansing, Mich.) — After decades of effort, scientists have finally managed to derive embryonic stem (ES) cells from cows and keep them in their primitive state in a dish. Access to these versatile cells, which can become all kinds of tissues, from skin to muscle to bone, could make it easier to tweak and preserve useful genetic traits of beef and dairy breeds. That in turn could lead to animals that produce more milk or more tender meat, face fewer complications in giving birth, or have greater resistance to diseases. The discovery might also open up new ways to study the cow’s basic development and to model human diseases.

“I thought I would never see this happen in my lifetime,” says Jose Cibelli, a developmental biologist at Michigan State University in East Lansing, who was part of a team that attempted to harvest bovine ES cells in the late 1990s. In those efforts and many others since, stem cells from cow embryos would develop into other cell types when grown in a lab dish, meaning that they would quickly lose their “stemmy-ness,” or pluripotency.

Researchers turned their eyes to cattle soon after the mouse gave up its ES cells in 1981, allowing researchers to study early embryonic development and test the effects of genetic defects. But other species have been more difficult. It would take researchers until 1998 to find the right broth of nutrients to culture human ES cells.

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By |February 6th, 2018|Uncategorized|0 Comments

Abeona’s Gene Therapy Gets FDA Regenerative Medicine Designation

Source: Epider Molysis Bulls News

(Cleveland, Ohio) — Abeona Therapeutics‘ EB-101, a gene therapy in development for patients with recessive dystrophic epidermolysis bullosa (RDEB), has received the regenerative medicine advanced therapy (RMAT) designation by the U.S. Food and Drug Administration (FDA).

The RMAT designation is attributed to promising “regenerative” therapies — cell therapies, tissue engineering, or cell and tissue products — that are supported by preliminary clinical data showing potential to advance the therapeutic care of unmet medical needs. The new designation is part of the 21st Century Cures Act, and opens the possibility of priority review and accelerated approvals by the FDA.

FDA’s decision was also supported by data from a Phase 1/2 clinical trial (NCT01263379) in which researchers used patients’ own skin cells (keratinocytes) to insert, using a virus, a correct version of the COL7A1 gene, which is defective in patients with epidermolysis bullosa. This led to the production of functional collagen protein.

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By |January 30th, 2018|Uncategorized|0 Comments

Novel Tissue Scaffolding Technique Helps Build Large Organs

Source: Gen News

(BRISTOL, England) — Researchers say they have developed a new tissue scaffold technology that could one day enable the engineering of large organs. The team led by the Universities of Bristol and Liverpool has shown that it is possible to combine cells with a special scaffold to produce living tissue in the laboratory. It is hoped this can then be implanted into patients as a way of replacing diseased parts of the body.

Until now, the approach has generally been limited to growing small pieces of tissue, as larger dimensions reduce the oxygen supply to the cells in the center.

The scientists used cartilage tissue engineering as a model system for testing a new method of overcoming the oxygen limitation problem. They synthesized a new class of artificial membrane binding proteins that can be attached to stems cells. By attaching an oxygen-carrying protein, myoglobin, to the stem cells before they are used to engineer cartilage, they ensure that each cell has its own oxygen reservoir that it can access when the oxygen in the scaffold drops to dangerously low levels.

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By |June 17th, 2015|Uncategorized|0 Comments

Mayo Clinic Opens New Regenerative Center

Source: PostBulletin.com

(ROCHESTER, New York) — Local officials hope a new ultra-clean laboratory in the Mayo Clinic Center for Regenerative Medicine will help draw businesses in the burgeoning field.

“It is one of the only few places of its kind on the planet available to companies,” said Gary Smith, president of Rochester Area Economic Development Inc. “These are expensive facilities to build, and a lot of companies can’t afford that capital investment.”

Having opened its doors to visitors only last week, final touches were being applied Tuesday to the sensitive equipment during a tour of the Advanced Product Incubator.

The 3,000-square-foot laboratory and office space anchors half of the third floor of the Minnesota Biobusiness Center. Because the API is hoping to attract business to Rochester in addition to developing therapies within the clinic, the facility was jointly funded by RAEDI, the city of Rochester and Mayo Clinic.

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By |June 17th, 2015|Uncategorized|0 Comments

Stem Cells Pass Safety Test In Vision-Loss Trial

Source: Nature // Photo: Retinal Cells Derived From Embryonic Cells

(MARLBOROUGH, Mass.) — A company that has spent more than 20 years trying to develop treatments based on embryonic stem cells is taking encouragement from small, preliminary tests of the cells in people with progressive vision loss. If the technique continues to impress in larger trials designed to assess its effectiveness, it could become the first therapy derived from embryonic stem cells to reach the market.

A study of four patients, published in Stem Cell Reports on 30 April1, shows that injection of retinal cells derived from stem cells is safe for people with macular degeneration. The report follows similar results from a trial in 18 patients that was published last October2.
Both studies were meant to assess safety only, and neither included a control group. In the latest study, conducted by researchers in Korea and the United States, three participants were able to read 9–19 more letters further on an eye chart a year after treatment — but two of the three also gained some ground in their untreated eyes.

“This bodes well,” says Robert Lanza, chief scientific officer at Ocata Therapeutics in Marlborough, Massachusetts, and an author of the study. “But I think we need to interpret this improvement cautiously until more controlled studies are done.”

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Research Report

By |April 30th, 2015|Uncategorized|0 Comments

Scientists Find Way To Monitor Stem Cells After Transplantation Into Brain

Source: Stanford University

(STANFORD, Ca.) — Investigators at the Stanford University School of Medicinehave devised a way to monitor neural stem cells after they’ve been transplanted into the brain.
The scientists were able to determine not only whether the stem cells transplanted into living animals survived but whether they matured into nerve cells, integrated into targeted brain circuits and, most important, were firing on cue and igniting activity in downstream nerve circuits.

The new monitoring technique could in principle be used to determine the success of other kinds of stem cell transplantations. It promises in the near term to improve researchers’ ability to optimize stem cell therapies in animal experiments and, in the intermediate term, to speed progress in human trials of stem cell replacement therapy, a promising but problem-plagued medical intervention.

Many disorders of the central nervous system, such as Parkinson’s disease, are characterized by defective nerve cells in specific brain regions. This makes disorders such as Parkinson’s excellent candidates for stem cell therapies, in which the defective nerve cells are replaced. But the experiments in which such procedures have been attempted have met with mixed results, and those conducting the experiments are hard put to explain them. There’s been no good way to evaluate what the transplanted stems cells are doing. So optimizing the regimens becomes a matter of guesswork and luck.

“That’s the key missing step in stem cell therapy design: Once you’ve transplanted the cells, you can’t tell exactly what they’re doing afterwards,” said Jin Hyung Lee, PhD, assistant professor of neurology, of neurosurgery and of bioengineering. In the case of brain-oriented therapies, you have to look for behavioral changes, she said. “And even when you see them, you still don’t know whether the newly transplanted cells integrated into the right brain circuits and are now functioning correctly there.”

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Research Report

By |April 30th, 2015|Uncategorized|0 Comments

New Study Finds Stem Cell Therapy via Intra-Carotid Artery Infusion Safe for Treatment of Stroke

Source: HealthCanal

(MIAMI, Fla.) — A yearlong study of patients who had suffered from ischemic strokes, led by physician-scientists at the Interdisciplinary Stem Cell Institute at the Miller School of Medicine, has found that stem cells can be safely infused to the brain through the carotid artery within two weeks after a stroke.

The national co-principal investigator of the study, Dileep R. Yavagal, M.D., associate professor of neurology at the Miller School, presented the discovery abstract of the RECOVER-Stroke trial entitled Intra-Arterial Delivery of Autologous ALDHbr Cells in Ischemic Stroke: Final 1-Year Results of the RECOVER-Stroke Trial at the European Stroke Organization Conference, in the UK. The findings provide new hope for future stroke treatments as well as for other brain-related illnesses.

“We are excited by the findings of the new study as it offers promise for stroke victims and for those with other neurological conditions,” says Yavagal, who is also Director of Interventional Neurology, Co-Director of Endovascular Neurology, associate professor of neurological surgery and a member of the Interdisciplinary Stem Cell Institute. “Previous thought was that stem cell use for brain conditions could lead to worsening stroke or even brain cancer. The conclusions of our research prove that stem cells are safe when given through the carotid artery with a small catheter to treat neurological illnesses, and we can continue to explore the efficacy of stem cells for treatments.”

After a full year of stem cell injections, no increased serious adverse effects were detected in any patients. Specifically, no ischemia-related neurologic worsening was seen as a result of the intra-carotid infusion of stem cells. The intra-arterial approach for cell delivery is worth pursuing for cell-based stroke therapy in future larger studies.

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By |April 28th, 2015|Uncategorized|0 Comments