Amelioration of diabetic retinopathy by engrafted human adipose-derived mesenchymal stem cells in streptozotocin diabetic rats

Abstract

Diabetic retinopathy is a common complication of diabetes, which is caused by injury to retinal microvasculature and neurons. Mesenchymal stem cells (MSCs), which proved to have multi-linkage differentiation capacity, including endothelial cells and neurons, might be a promising cell therapy resource. The current pilot study was performed using the streptozotocin (STZ) rat model of diabetic retinopathy injected intravenously with human adipose-derived mesenchymal stem cells (AMSCs) in an effort to investigate the potency and possible therapeutic effects of AMSCs. Four experimental groups of Wistar rats were included in the current study: an untreated control group of STZ diabetic rats (n = 10), a normal non-diabetic control group (n = 20), an AMSC therapy group of STZ diabetic rats (n = 50), and a sham group of STZ diabetic rats (n = 50). Blood glucose levels were monitored closely. Immunofluorescence was used to study AMSC distribution and differentiation. The integrity of the blood-retinal barrier (BRB) was evaluated by Evans blue dye infusion to evaluate the therapeutic effects. After 1 week of transplantation, a significant reduction in blood glucose levels was observed in the AMSC therapy group relative to the sham group. BRB integrity was also improved, as less Evans blue dye leakage was observed. Donor cells were observed in the retinas of therapy group rats, and they expressed rhodopsin and glial fibrillary acidic protein (GFAP), specific markers for photoreceptors and astrocytes, respectively. Taken together, the results of the current study suggest that AMSCs may improve the integrity of the BRB in diabetic rats by differentiation into photoreceptor and glial-like cells in the retina and by reducing the blood glucose levels. Furthermore, the data presented herein provide evidence that AMSCs may serve as a promising therapeutic approach for diabetic retinopathy.