Stem Cell Treatments for Diabetic Retinopathy


Research by a team at the University of Virginia School of Medicine provided a crucial piece to treating patients who suffer vision loss because of diabetic retinopathy, a condition that affects millions of people with diabetes. The UVA team showed that the best for adult stem cells to treat this condition are cells taken from donors who do not suffer diabetes rather than cells taken from patients’ own bodies. This work could provide a critical step toward injecting stem cells into patients’ eyes to stop or even reverse vision loss. These findings could also establish a crucial framework for evaluating stem cells to be used in potential future treatments for diabetic retinopathy.

Diabetic Retinopathy

“It answers a vital question: If we’re going to carry this therapy forward into clinical trials, where are we going to get the best bang for the buck?” said UVA researcher and ophthalmologist Paul Yates, M.D., Ph.D. “The answer seems to be, probably, taking cells from patients who aren’t diabetic. Because the diabetic stem cells don’t seem to work quite as well. And that’s not terribly surprising, because we already know that this cell type is damaged by diabetes.”

The researchers hope to use stem cells derived from fat, since they are harvested during liposuction procedures. These fat-based stem cells might be able to stop or greatly delay the vascular degeneration that eventually leads to blindness in patients with diabetic retinopathy. What are the best cells for the job in this case? UVA’s new research provides those important answers. “We now know what to look for when we harvest a patient’s cells, because we know what distinguishes good quality cells from poor quality,” said researcher Shayn M. Peirce, Ph.D., of the UVA Department of Biomedical Engineering. “We almost have a screen to determine quality control. We’re essentially establishing quality-control criteria by understanding what works and why.”

Diabetic retinopathy patients desperately need new and more effective treatments. First of all, there are a growing number of people with this condition and secondly the present treatments only show limited effectiveness. More than 100 million people are estimated to suffer from diabetic retinopathy and related conditions; current treatments use lasers to fight back invading blood vessels, but these treatments often destroy much of the retina. Alternatively, patients are required to receive injections of anti-blood vessel forming drugs such as Lucentis (ranibizumab) or Eylea (aflibercept) directly into their eyeball, sometimes every month, for the rest of their lives.

“There’s huge room for improvement on the standard of care, and the number of patients in this demographic is increasing by the day, dramatically, so the need is only going up,” Peirce said. “So I think there are three pieces working together — UVA’s strengths in this area, the FDA’s encouragement [of stem cell research in the eye] and the clinical realities — to drive this cell-based therapy toward the clinic.”

While much more work needs to be done, if all goes well, the UVA team hopes to begin clinical trials in humans within the next few years. “This is not science fiction at all,” Yates said. “The idea that you can take cells from somewhere else and inject them into the eye to treat disease is here today.”

Vascular Progenitors Made from Induced Pluripotent Stem Cells Repair Blood Vessels in the Eye Regardless of the Site of Injection


Johns Hopkins University medical researchers have reported the derivation of human induced-pluripotent stem cells (iPSCs) that can repair damaged retinal vascular tissue in mice. These stem cells, which were derived from human umbilical cord-blood cells and reprogrammed into an embryonic-like state, were derived without the conventional use of viruses, which can damage genes and initiate cancers. This safer method of growing the cells has drawn increased support among scientists, they say, and paves the way for a stem cell bank of cord-blood derived iPSCs to advance regenerative medical research.

In a report published Jan. 20 in the journal Circulation, Johns Hopkins University stem cell biologist Elias Zambidis and his colleagues described laboratory experiments with these non-viral, human retinal iPSCs, that were created generated using the virus-free method Zambidis first reported in 2011.

“We began with stem cells taken from cord-blood, which have fewer acquired mutations and little, if any, epigenetic memory, which cells accumulate as time goes on,” says Zambidis, associate professor of oncology and pediatrics at the Johns Hopkins Institute for Cell Engineering and the Kimmel Cancer Center. The scientists converted these cells to a status last experienced when they were part of six-day-old embryos.

Instead of using viruses to deliver a gene package to the cells to turn on processes that convert the cells back to stem cell states, Zambidis and his team used plasmids, which are rings of DNA that replicate briefly inside cells and then are degraded and disappear.

Next, the scientists identified and isolated high-quality, multipotent, vascular stem cells that resulted from the differentiation of these iPSC that can differentiate into the types of blood vessel-rich tissues that can repair retinas and other human tissues as well. They identified these cells by looking for cell surface proteins called CD31 and CD146. Zambidis says that they were able to create twice as many well-functioning vascular stem cells as compared with iPSCs made with other methods, and, “more importantly these cells engrafted and integrated into functioning blood vessels in damaged mouse retina.”

Working with Gerard Lutty, Ph.D., and his team at Johns Hopkins’ Wilmer Eye Institute, Zambidis’ team injected these newly iPSC-derived vascular progenitors into mice with damaged retinas (the light-sensitive part of the eyeball). The cells were injected into the eye, the sinus cavity near the eye or into a tail vein. When Zamdibis and his colleagues took images of the mouse retinas, they found that the iPSC-derived vascular progenitors, regardless of injection location, engrafted and repaired blood vessel structures in the retina.

“The blood vessels enlarged like a balloon in each of the locations where the iPSCs engrafted,” says Zambidis. Their vascular progenitors made from cord blood-derived iPSCs compared very well with the ability of vascular progenitors derived from fibroblast-derived iPSCs to repair retinal damage.

Zambidis says that he has plans to conduct additional experiments in diabetic rats, whose conditions more closely resemble human vascular damage to the retina than the mouse model used for the current study, he says.

With mounting requests from other laboratories, Zambidis says he frequently shares his cord blood-derived iPSC with other scientists. “The popular belief that iPSCs therapies need to be specific to individual patients may not be the case,” says Zambidis. He points to recent success of partially matched bone marrow transplants in humans, shown to be as effective as fully matched transplants.

“Support is growing for building a large bank of iPSCs that scientists around the world can access,” says Zambidis, although large resources and intense quality-control would be needed for such a feat. However, Japanese scientists led by stem-cell pioneer Shinya Yamanaka are doing exactly that, he says, creating a bank of stem cells derived from cord-blood samples from Japanese blood banks.

Treating Diabetic Retinopathy with Stem Cells


Scientists at Queen’s University Belfast hope to design a new approach for treating the eyesight of diabetic patients by using adult stem cells.

Millions of diabetics every year are at risk for losing their eyesight due to diabetic retinopathy. When high blood sugar causes blood vessels in the eye to leak or become blocked, failed blood flow damages the retina and lead to vision impairment. If left untreated, diabetic retinopathy can lead to blindness.

The Queen’s University Belfast group have initiated the REDDSTAR study, which stands for Repair of Diabetic Damage by Stromal Cell Administration, and this study involves researchers from the Queen’s Center for Vision and Vascular Science in the School of Medicine, Dentistry and Biomedical Sciences. REDDSTAR begins with the isolation of stem cells from patients and expanding them in the laboratory. Then these patient-specific cells are delivered to the patient from whom they were originally drawn in order to repair the blood vessels in the eye. This blood vessel repair is especially useful in patients with diabetic retinopathy.

Presently, diabetic retinopathy is treated with laser ablation of new blood vessels that grow in response to damage. These new blood vessels become so dense that they obscure vision. However, presently, there are no treatments to control the progression of diabetic complications.

Alan Stitt, the director of the Centre for Vision and Vascular Science at Queen’s and lead scientist for the REDDSTAR study, said, “The Queen’s component of the REDDSTAR study involves investigating the potential of a unique stem cell population to promote repair of damaged blood vessels in the retina during diabetes.” Professor Stitt continued: “The impact could be profound for patients, because regeneration of damaged retina could prevent progression of diabetic retinopathy and reduce the risk of vision loss.”

“Treatments for diabetic retinopathy are not always satisfactory. They focus on end-stages and fail to address the root causes of the condition. A novel, alternative therapeutic approach is to harness adult stem cells to promote regeneration of the damaged retinal blood vessels and thereby prevent and/or reverse retinopathy.”

Stitt said the new research project is one of several regenerative medicine approaches ongoing at his research center. Their approach is to isolate a rather well-defined population of stem cells and then deliver those stem cells to sites in the body that have been ravaged by diabetes. In particular patients, these strategies have produced remarkable benefits from stem cell-mediated repair of their blood vessels. Treatments such as this one are simply the first step in the quest to develop exciting, effective and new therapies in an area of medicine where such therapies are desperately needed.

In the REDDSTAR study, stem cells from bone marrow are used and these stem cells are provided by Orbsen Therapuetics, which is a spin-off from the Science Foundation Ireland-funded Regenerative Medicine Institute (REMEDI) at NUI Galway.

This project will design protocols for growing these bone marrow-derived stem cells and they will be tested in several preclinical models of diabetes and diabetic complications at research centers in Belfast, Galway, Munich, Berlin, and Porto before human clinical trails take place in Denmark.

Queen’s Centre for Vision and Vascular Science is a key focus of the University’s ambitious 140-million pound “together we can go Beyond” fundraising campaign. This campaign is due to expand the Vision Science program further when the University’s new 32-million pound Wellcome-Wolfson Centre for Experimental Medicine opens in 2015. Along with vision, two new programs in Diabetes and Genomics will also be established in the new Center. These Center should stimulate further investment and global collaborations between biotech and health companies in Ireland.