Exploring the Use of Stem Cells in Fat to Repair Damage From Diabetic Retinopathy

November 17, 2015

Research at the University of Tennessee Health Sciences could lead to human trials in the next 2 to 3 years.

Rajashekhar Gangaraju, PhD, has seen the devastating effects of diabetes firsthand. Both his father and grandfather suffered from the disease, as well as vision loss that results from long-term damage to blood vessels in the eyes.

Now an assistant professor at the University of Tennessee Health Science Center in Memphis, Gangaraju has relocated from Indiana School of Medicine—along with a $1-million grant from the National Eye Institute—to continue his quest to halt the damage that diabetes causes. His method? Repair the damage with stem cells, using a plentiful source: fat tissue.


As diabetes progresses, elevated blood sugar levels damage the blood vessels that carry nutrients to the retina. As a result, the blood vessels leak and bleed and can no longer do their job. Although the body compensates by producing more blood vessels, these are poor substitutes and leak as well, and the damage perpetuates. Hemorrhaging, retinal detachment, and blindness can result.1

According to the CDC, the number of Americans with vision-threatening diabetic retinopathy (DR) is projected to triple between 2005 and 2050, from 1.2 million to 3.4 million, due to an aging population and the rising incidence of diabetes.2 With the increasing number of diabetes cases around the globe, the threat of vision loss is a worldwide problem.3

Treatment for DR may not occur right away. Many patients may not realize that the symptoms they are experiencing are of DR; they may attribute vision problems to cataracts or aging, which are comparatively easier to address. Once the condition progresses to diabetic macular edema (DME) treatments include injections with vascular endothelial growth factor (VEGF) inhibitors, which block the protein VEGF; this prevents abnormal blood vessels from growing and leaking fluid. While these injections represent a vast improvement over earlier available treatments, they still require repeat visits over an extended period and can be expensive.1,4 Gangaraju sought an alternative treatment that would begin earlier and have longer-lasting effects.


In a 2014 paper, Gangaraju outlines the possibilities that stem cell therapy could offer for patients with diabetes suffering vision loss. He explains that DR results from the loss of pericytes, the connective tissues found in the walls of small blood vessels of the eye, and discusses their role as mediators of DR and potential targets for treatment.5

The key to treatment, he explains in the paper, is the discovery that adipose stem cells—which are located in fat tissue—could be used as a resource for regenerating damaged blood vessels in the retina. Unlike other potential sources of stem cells, such as bone marrow, adipose tissue is easily obtained and cells derived from it can counteract what is occurring in the blood vessels of an individual with diabetes.

“We know that the stem cells are migrating toward the blood vessels and are trying to arrest the leakage. We believe this will be a therapy helpful for early stage diabetics or those who have begun to suffer the effects of diabetes and have early vision loss due to the leaking blood vessels,” Gangaraju said in a statement when the grant was announced.6


For all the promise of stem-cell therapy, Gangaraju told Evidence-Based Diabetes Management that he is being extraordinarily careful before he moves into his first clinical trials with humans. (Some trials for ocular conditions are already taking place in Europe and in Mexico.) As he explained, there are many questions that must be answered: Are the cells being rejected by the host? Are there any tumors? In addition, there is the key question: how long do the effects last?

That last part is important because if it turns out that stem cell repair for retinopathy offers a long-term solution, it could represent a significant advance over current treatment with VEGF inhibitors.

This will require gaining a richer understanding of exactly how the stem cells are restoring vision in the eye. “We need to answer the question, ‘What is the mechanism of action?’”Gangaraju pointed out. Although he is certainly aware of treatments taking place in Mexico for DME, because the mechanism of action is not well understood, this is simply too risky. He will take his time and wants to understand the potential for stem cell therapy on the retina. “I’m a back-of-the-eyes guy,” he said.

There’s hope this work will lead to a preventive measure that can be used instead of waiting for vision to deteriorate. Once Gangaraju has enough information, he can present it to the National Institutes of Health and seek approval from the FDA for the first clinical trials with humans. He expects this to happen in the next 2 to 3 years.References

1. Facts about diabetic eye disease. National Eye Institute website. https://nei.nih.gov/health/diabetic/retinopathy. Accessed September 25, 2015.

2. Saaddine JB, Honeycutt AA, Narayan KM, Zhang X, Klein R, Boyle JP. Vision Health Initiative Report. Projection of diabetic retinopathy and other major eye diseases among people with diabetes mellitus in the United States, 2005-2050. CDC website. http://www.cdc.gov/visionhealth/publications/diabetic_retinopathy.htm. Updated August 24, 2009. Accessed September 25, 2015.

3. Hu FB. Globalization of diabetes: the role of diet, lifestyle and genes. Diabetes Care. 2011;34(6):1249-1257. doi: 10.2337/dc11-0442.

4. Caffrey MK. Patients lack awareness of how diabetes can damage vision. Am J Manag Care. 2015;21(SP9):SP315.

5. Rajashekhar G. Mesenchymal stem cells: new players in retinopathy therapy. Front Endocrinol (Lausanne). 2014;5(59). doi: 10.3389/fendo.2014.00059.

6. Assistant professor Rajashekhar Gangaraju UTHSC receives $1 million grant to continue diabetic retinopathy research [press release]. Memphis, TN: UTHSC Communications and Marketing; August 5, 2015. http://news.uthsc.edu/assistant-professor-rajashekhar-gangaraju-uthscreceives-1-million-grant-continue-diabetic-retinopathyresearch/.August 6, 2015.