Perivascular Progenitor Cells Derived from Human Embryonic Stem Cells Exhibit Functional Characteristics of Pericytes, and Improve the Retinal Vasculature in a Rodent Model of Diabetic Retinopathy. Homo sapiens

Diabetic retinopathy (DR) is the leading cause of blindness in working-age people. Pericyte loss is one of the pathologic cellular events in DR, which weakens the retinal microvessels. Damages to the microvascular networks are irreversible and permanent, thus further progression of DR is inevitable. In this study, we hypothesize that multipotent perivascular progenitor cells derived from human ESCs (hESC-PVPCs) improve the damaged retinal vasculature in the streptozotocin (STZ)-induced diabetic rodent models. We describe a highly efficient and feasible protocol to derive such cells using a natural selection method without cell sorting processes. As a cellular model of pericytes, hESC-PVPCs exhibited marker expressions such as CD140B, CD146, NG2, and functional characteristics of pericytes. Following a single intravitreal injection into diabetic Brown Norway (BN) rats, we demonstrate that the cells localized alongside typical perivascular regions of the retinal vasculature, and stabilized blood-retinal barrier (BRB) breakdown. Findings in this study highlight a therapeutic potential of hESC-PVPCs in DR by mimicking the role of pericytes in vascular stabilization. Overall design: The molecular profiling analysis of ontological selected gene sets demonstrated that the transcripts associated with stemness markers, neural crest, neuro-ectoderm, and endoderm gene expressions.