ADIPOSE STEM CELLS FOR BLOOD-RETINAL BARRIER REPAIR.

In the last few decades, adipose-derived mesenchymal stem cells (ASCs) have been widely investigated in the field of regenerative medicine because of their multipotent differentiation ability. In fact, they can give rise not only to elements of mesodermal origin, but also to elements of different cell lines such as neurons or glial cells. In the present work, we tested a pericyte (PC) differentiation of ASCs in order to provide a tool to overcome the massive PC loss occurring in cases of diabetic retinopathy, characterized by the blood-retinal barrier (BRB) impairment due to altered interactions between endothelial cells and PCs. To this aim, pericyte-like ASCs (P-ASCs) were obtained by growing them in a specific PC medi- um. In addition, some samples of P-ASCs were cultured in high glucose (HG) conditions to mimic the altered microenvironment of a diabetic eye. Their possible beneficial effects were assessed in co-cultures of P-ASCs and human retinal endothelial cells (HRECs). Results obtained by immunofluorescence techniques show that, compared to native ASCs, the presence of P-ASCs induced an increased endothelial expression of junction proteins (VE-cadherin and ZO-1), suggesting an improved BRB integrity, as also indicated by higher values of trans-endothelial electrical resistance. Moreover, by three-dimensional co-cultures carried out in Matrigel, it was possible to demonstrate that P-ASCs were preferentially positioned in the same location as native PCs, i.e. around the typical tubular, vessel-like structures formed by HRECs. It can be concluded that P-ASCs may represent a valuable tool to develop therapeutic strategies to counteract BRB disruption in case of diabetic retinopathy.