An injection of stem cells into the eye may soon slow or reverse the effects of early-stage age-related macular degeneration, according to new research from scientists at Cedars-Sinai. Currently, there is no treatment that slows the progression of the disease, which is the leading cause of vision loss in people over 65.

"This is the first study to show preservation of vision after a single injection of adult-derived human cells into a rat model with age-related macular degeneration," said Shaomei Wang, MD, PhD, lead author of the study published in the journal STEM CELLS and a research scientist in the Eye Program at the Cedars-Sinai Board of Governors Regenerative Medicine Institute.

The stem cell injection resulted in 130 days of preserved vision in laboratory rats, which roughly equates to 16 years in humans.

Age-related macular degeneration affects upward of 15 million Americans. It occurs when the small central portion of the retina, known as the macula, deteriorates. The retina is the light-sensing nerve tissue at the back of the eye. Macular degeneration may also be caused by environmental factors, aging and a genetic predisposition.

When animal models with macular degeneration were injected with induced neural progenitor stem cells, which derive from the more commonly known induced pluripotent stem cells, healthy cells began to migrate around the retina and formed a protective layer. This protective layer prevented ongoing degeneration of the vital retinal cells responsible for vision.

Cedars-Sinai researchers in the Induced Pluripotent Stem Cell (iPSC) Core, directed by Dhruv Sareen, PhD, with support from the David and Janet Polak Foundation Stem Cell Core Laboratory, first converted adult human skin cells into powerful induced pluripotent stem cells (iPSC), which can be expanded indefinitely and then made into any cell of the human body. In this study, these induced pluripotent stem cells were then directed toward a neural progenitor cell fate, known as induced neural progenitor stem cells, or iNPCs.

"These induced neural progenitor stem cells are a novel source of adult-derived cells which should have powerful effects on slowing down vision loss associated with macular degeneration," said Clive Svendsen, PhD, director of the Board of Governors Regenerative Medicine Institute and contributing author to the study. "Though additional pre-clinical data is needed, our institute is close to a time when we can offer adult stem cells as a promising source for personalized therapies for this and other human diseases."

Next steps include testing the efficacy and safety of the stem cell injection in preclinical animal studies to provide information for applying for an investigational new drug. From there, clinical trials will be designed to test potential benefit in patients with later-stage age-related macular degeneration.

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The above story is based on materials provided by Cedars-Sinai Medical Center. Note: Materials may be edited for content and length.

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Stem cell injection may soon reverse vision loss caused by age-related macular degeneration

LOS ANGELES (EMBARGOED UNTIL 7 A.M. EDT on APRIL 14, 2015) - An injection of stem cells into the eye may soon slow or reverse the effects of early-stage age-related macular degeneration, according to new research from scientists at Cedars-Sinai. Currently, there is no treatment that slows the progression of the disease, which is the leading cause of vision loss in people over 65.

"This is the first study to show preservation of vision after a single injection of adult-derived human cells into a rat model with age-related macular degeneration," said Shaomei Wang, MD, PhD, lead author of the study published in the journal STEM CELLS and a research scientist in the Eye Program at the Cedars-Sinai Board of Governors Regenerative Medicine Institute.

The stem cell injection resulted in 130 days of preserved vision in laboratory rats, which roughly equates to 16 years in humans.

Age-related macular degeneration affects upward of 15 million Americans. It occurs when the small central portion of the retina, known as the macula, deteriorates. The retina is the light-sensing nerve tissue at the back of the eye. Macular degeneration may also be caused by environmental factors, aging and a genetic predisposition.

When animal models with macular degeneration were injected with induced neural progenitor stem cells, which derive from the more commonly known induced pluripotent stem cells, healthy cells began to migrate around the retina and formed a protective layer. This protective layer prevented ongoing degeneration of the vital retinal cells responsible for vision.

Cedars-Sinai researchers in the Induced Pluripotent Stem Cell (iPSC) Core, directed by Dhruv Sareen, PhD, with support from the David and Janet Polak Foundation Stem Cell Core Laboratory, first converted adult human skin cells into powerful induced pluripotent stem cells (iPSC), which can be expanded indefinitely and then made into any cell of the human body. In this study, these induced pluripotent stem cells were then directed toward a neural progenitor cell fate, known as induced neural progenitor stem cells, or iNPCs.

"These induced neural progenitor stem cells are a novel source of adult-derived cells which should have powerful effects on slowing down vision loss associated with macular degeneration," said Clive Svendsen, PhD, director of the Board of Governors Regenerative Medicine Institute and contributing author to the study. "Though additional pre-clinical data is needed, our institute is close to a time when we can offer adult stem cells as a promising source for personalized therapies for this and other human diseases."

Next steps include testing the efficacy and safety of the stem cell injection in preclinical animal studies to provide information for applying for an investigational new drug. From there, clinical trials will be designed to test potential benefit in patients with later-stage age-related macular degeneration.

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Additional Cedars-Sinai authors include Dhruv Sareen, PhD; Yuchun Tsai, PhD; Bin Lu, MD, PhD; Benjamin Bakondi, PhD; Sergey Girman, PhD; and Anais Sahabian, PhD.

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Stem cell injection may soon reverse vision loss due to age-related macular degeneration

New $6.4M federal grant support will fuel the development of 'guts in a dish' to study interaction between cells & microbes in both health and disease

IMAGE:These HIO structures, each about the size of a BB and grown from stem cells, allow scientists to study the interaction between the cells of the gut lining and microbes... view more

Credit: University of Michigan Medical School

ANN ARBOR, Mich. -- If you got hit with any of the 'intestinal bugs' that went around this winter, you've felt the effects of infectious microbes on your digestive system.

But scientists don't fully understand what's going on in gut infections like that - or in far more serious ones that can kill. Many mysteries remain in the complex interaction between our own cells, the helpful bacteria that live inside us, and tiny invaders.

Now, a team of University of Michigan scientists will tackle that issue in a new way. Using human stem cells, they'll grow tiny "guts in a dish" in the laboratory and study how disease-causing bacteria and viruses affect the microbial ecosystem in our guts. The approach could lead to new treatments, and aid research on a wide range of diseases.

This work was started as part of the U-M Medical School's self-funded Host Microbiome Initiative and Center for Organogenesis, and the U-M Center for Gastrointestinal Research, funded by the National Institutes of Health. It also received funding from the U-M's MCubed initiative for interdisciplinary work.

Now, the project has received a $6.4 million boost with a new five-year NIH grant.

It will allow the U-M team to expand their effort to grow human intestinal organoids, or HIOs - tiny hollow spheres of cells into which they can inject a mix of bacteria. They'll work with researchers at other institutions, as part of the Novel, Alternative Model Systems for Enteric Diseases, or NAMSED, initiative sponsored by the NIH's National Institute of Allergy and Infectious Diseases.

Balls of cells become mini-guts

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To fight nasty digestive bugs, scientists set out to build a better gut -- using stem cells

ANN ARBOR--Research led by the University of Michigan Life Sciences Institute has identified a gene critical to controlling the body's ability to create blood cells and immune cells from blood-forming stem cells--known as hematopoietic stem cells.

The findings, scheduled for online publication in the Journal of Clinical Investigation April 13, provide new insights into the underlying mechanics of how the body creates and maintains a healthy blood supply and immune system, both in normal conditions and in situations of stress--like the body experiences following a bone marrow transplant.

Along with helping scientists better understand the body's basic processes, the discovery opens new lines of inquiry about the Ash1l gene's potential role in cancers known to involve other members of the same gene family, like leukemia, or those where Ash1l might be highly expressed or mutated.

"It's vital to understand how the basic, underlying mechanisms function in a healthy individual if we want to try to develop interventions for when things go wrong," said study senior author Ivan Maillard, an associate research professor at the Life Sciences Institute, where his lab is located, and an associate professor in the Division of Hematology-Oncology at the U-M Medical School.

"Leukemia is a cancer of the body's blood-forming tissues, so it's an obvious place that we plan to look at next. If we find that Ash1l plays a role, then that would open up avenues to try to block or slow down its activity pharmacologically," he said.

Graduate students Morgan Jones and Jennifer Chase were the study's first authors.

Dysfunction of blood-forming stem cells is well known in illnesses like leukemia and bone marrow failure disorders. Blood-forming stem cells can also be destroyed by high doses of chemotherapy and radiation used to treat cancer. The replacement of these cells through bone marrow transplantation is the only widely established therapy involving stem cells in human patients.

But even in the absence of disease, blood cells require constant replacement--most blood cells last anywhere from a few days to a few months, depending on their type.

Over more than five years, Maillard and his collaborators identified a previously unknown but fundamental role played by the Ash1l gene in regulating the maintenance and self-renewal potential of these hematopoietic stem cells.

The Ash1l (Absent, small or homeotic 1-like) gene is part of a family of genes that includes MLL1 (Mixed Lineage Leukemia 1), a gene that is frequently mutated in patients who develop leukemia. The research found that both genes contribute to blood renewal; mild defects were seen in mice missing one or the other, but lacking both led to catastrophic deficiencies.

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U-M researchers find new gene involved in blood-forming stem cells

Mesenchymal stem cells captured in microcapsules. Each microcapsule is roughly 40 micrometers across.

A team of Cornell scientists has shown that stem cells confined inside tiny capsules secrete substances that help heal simulated wounds in cell cultures, opening up new ways of delivering these substances to locations in the body where they can hasten healing.

The capsules need to be tested to see if they help healing in animals and humans, but they could eventually lead to living bandage technologies: wound dressings embedded with capsules of stem cells to help the wound regenerate.

Microencapsulated equine mesenchymal stromal cells promote cutaneous wound healing in vitro appeared in the April 10Stem Cell Research & Therapy.

The encapsulation seems to increase the stem cells regenerative potential, said Gerlinde Van de Walle of the Baker Institute for Animal Health in the College of Veterinary Medicine, adding that the reasons why are not yet known. It's possible that putting them in capsules changes the interactions between stem cells or changes the microenvironment.

To her knowledge, Van de Walle said, this is the first time encapsulated stem cells have been used to treat wounds. Her team used horse stem cells and cell cultures because, unlike mice, the healing process in horses shares important similarities with the healing process in humans and because wound healing in horses is a particularly difficult problem in veterinary medicine.

Mesenchymal stem cells are adult stem cells that can be isolated from different parts of the body, and its long been known that they secrete substances that aid in tissue healing. Problems arise when trying to use these stem cells in real patients, Van de Walle said, because they often wont stay put in the healing area and can occasionally form tumors or develop into unwanted cell types. She and her team began exploring the possibilities of encapsulating these cells as a way of avoiding these pitfalls. The capsules help cells stay in place while they secrete substances into the wound and can be removed easily if the stem cells would develop in an adverse way.

The researchers collaborated with Mingling Ma of the Department of Biological and Environmental Engineering and his laboratory to create the coreshell hydrogel microcapsules around the stem cells

Van de Walle says she was excited to see that the capsules did not abolish the stem cell properties but instead appeared to enhance the beneficial effects the stem cell secreted products have on tissue cultures. This suggests that encapsulating the stem cells for wound healing not only avoids certain problems, it can boost the effectiveness of treatment.

With their mesenchymal stem cell work, Van de Walle and her colleagues are trying to understand the basic science behind the regenerative abilities of these cells.

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Encapsulated stem cells accelerate wound healing