Abstract
A pericyte-like differentiation of human adipose-derived mesenchymal stem cells (ASCs) was tested in in vitro experiments for possible therapeutic applications in cases of diabetic retinopathy (DR) to replace irreversibly lost pericytes. For this purpose, pericyte-like ASCs were obtained after their growth in a specific pericyte medium. They were then cultured in high glucose conditions to mimic the altered microenvironment of a diabetic eye. Several parameters were monitored, especially those particularly affected by disease progression: cell proliferation, viability and migration ability; reactive oxygen species (ROS) production; inflammation-related cytokines and angiogenic factors. Overall, encouraging results were obtained. In fact, even after glucose addition, ASCs pre-cultured in the pericyte medium (pmASCs) showed high proliferation rate, viability and migration ability. A considerable increase in mRNA expression levels of the anti-inflammatory cytokines transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) was observed, associated with reduction in ROS production, and mRNA expression of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), and angiogenic factors. Finally, a pmASC-induced better organization of tube-like formation by retinal endothelial cells was observed in three-dimensional co-culture. The pericyte-like ASCs obtained in these experiments represent a valuable tool for the treatment of retinal damages occurring in diabetic patients.
Highlights
Multipotent differentiation ability of human adipose-derived mesenchymal stem cells (ASCs) has been extensively studied in the last few decades for their potential applications in stem-cell-based therapeutic strategies
Hyperglycemia triggers a series of events that include inflammation, mitochondrial overproduction of reactive oxygen species (ROS), neoangiogenesis and blood retinal barrier (BRB) breakdown
It is widely accepted that pericyte loss is a major cause of microvasculature damage, as it occurs in diabetic retinopathy (DR) patients
Summary
Multipotent differentiation ability of human adipose-derived mesenchymal stem cells (ASCs) has been extensively studied in the last few decades for their potential applications in stem-cell-based therapeutic strategies They are able to differentiate into cells of mesodermal origin such as adipocytes [1,2], chondrocytes [3] and osteocytes [4], and into cells of different lineages [5]. Co-cultures of pericyte-like differentiated ASCs and human retinal endothelial cells (HRECs) induced an increased expression of junction proteins. From here on, they will be called pmASCs because their differentiation process was achieved by using PM. Positive effects were observed for HREC tube-like formations
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