Adipose-Derived Stem Cells from Diabetic Sources Show Impaired Vascular Stabilization in the Treatment of Diabetic Retinopathy

Diabetic retinopathy is a debilitating disease that leads to progressive retinal vascular pathologies and ultimately to vision loss which current treatments are unable to reverse. We have recently shown that intra-vitreal injection of adipose-derived stem cells (ASCs) stabilize retinal microvasculature and encourage regeneration of damaged capillary beds in several mouse models of retinal vasculopathy. ASCs are advantageous because of their relative ease of harvest from accessible fat depots, as well as their potential for autologous or allogeneic treatment. Understanding the status of ASCs harvested from diabetic patients is of critical importance for moving forward with autologous therapies. Using the hyperglycemic Akimba mouse model of diabetic retinopathy, we probed the differences in treatment efficacy and function of mouse adipose-derived stem cells (mASCs) derived from healthy vs. diabetic Akimba mice. Akimba mice received intra-vitreal injections of DiI-labeled mASCs, and retinae were imaged four weeks later by confocal microscopy. mASCs from healthy, non-diabetic mice were more effective than diabetic mASCs in protecting the diabetic retina from vascular dropout. mASC viability was assessed using TUNEL and EdU incorporation assays, which revealed that healthy mASCs proliferate more rapidly and undergo less apoptosis than diabetic mASCs. Finally, when compared to diabetic mASCs, healthy mASCs secreted more angiogenesis-promoting factors as determined by high-throughput ELISA. Our findings suggest that injected ASCs derived from diabetic mice have a decreased ability to affect the retinal vasculature likely due to decreased cell viability and secretion of angiogenic factors, and support the utility of an allogeneic approach in the clinical arena.