Treatment of Diabetic Retinopathy With Adipose-Derived Stem Cells
Mendel, Thomas, Experimental Pathology - Graduate School of Arts and Sciences, University of Virginia
Yates, Paul, Department of Ophthalmology, University of Virginia
Diabetic retinopathy threatens the vision of over 100 million people in the world. Retinal pericytes are critical cells that enshealth and protect the delicate retinal microvasculature via direct contact and paracrine mechanisms. After diabetes causes pericyte dysfunction over decades with the disease, a cascade of microvascular pathology ensues that results in blindness. Current therapies aid patients with their symptoms, but do not address the fundamental cellular biology of diabetic retinopathy.
Mesenchymal stem cells, found throughout the body, are capable of acting as pericytes. This suggests that they may be useful as a protective and regenerative cellular therapy for retinal vascular disease, applied in a way that is mindful of the underlying cellular pathology. Easily harvested from adipose, these stem cells may serve as a regenerative cure for diabetic retinopathy.
Our work demonstrated, for the first time, that adipose-derived stem cells are capable of engraftment into multiple pre-clinical models of diabetic retinopathy, where they appear and function like pericytes to stabilize retinopathy, sometimes dramatically. These models included short experimental times of only a few days as well as longer experiments, which revealed transplanted stem cells adopting pericyte morphology along vessels.
Over the course of our experiments, we came to appreciate the impact that the transplanted stem cells could have via paracrine signaling, even without full engraftment and microvascular contact. We also discovered that the diabetic status of the stem cell donor impacted the signaling and disease-modulating efficacy of the cells transplanted into the eye.
While clarity is difficult to find in the field of mesenchymal stem cell research, largely due to its relative youth as a field of study, these experiments confirm the bright promise that stem cell therapy holds for degenerative diseases. Further work should be directed towards understanding the relationship between mesenchymal stem cells and pericytes, as well as investigating precisely how they control their own differentiation and interaction with their surrounding microenvironment.
PHD (Doctor of Philosophy)
stem cells, retinopathy, diabetes, pericytes
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