Journal
STEM CELLS TRANSLATIONAL MEDICINE
Volume 5, Issue 9, Pages 1268-1276Publisher
WILEY
DOI: 10.5966/sctm.2015-0342
Keywords
Human embryonic stem cells; Perivascular progenitor cells; Pericytes; Diabetic retinopathy; Blood-retinal barrier
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Funding
- Bio and Medical Technology Development Program of the National Research Foundation [2011-0019487]
- Ministry for Health and Welfare by the Korean government [HI14C3365]
- National Research Foundation of Korea [2011-0019487] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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. Damage to the microvascular networks is irreversible and permanent; thus further progression of DR is inevitable. In this study, we hypothesize that multipotent perivascular progenitor cells derived from human embryonic stem cells (hESC-PVPCs) improve the damaged retinal vasculature in the streptozotocin-induced diabetic rodent models. We describe a highly efficient and feasible protocol to derive such cells with 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 rats, we demonstrate that the cells localized alongside typical perivascular regions of the retinal vasculature and stabilized the blood-retinal barrier breakdown. Findings in this study highlight a therapeutic potential of hESC-PVPCs in DR by mimicking the role of pericytes in vascular stabilization. SIGNIFICANCE This study provides a simple and feasible method to generate perivascular progenitor cells from human embryonic stem cells. These cells share functional characteristics with pericytes, which are irreversibly lost at the onset of diabetic retinopathy. Animal studies demonstrated that replenishing the damaged pericytes with perivascular progenitor cells could restore retinal vascular integrity and prevent fluid leakage. This provides promising and compelling evidence that perivascular progenitor cells can be used as a novel therapeutic agent to treat diabetic retinopathy patients.
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