Background: Endothelial progenitor cell (EPC) transplantation is a promising therapy for ischemic diseases such as\nischemic myocardial infarction and hindlimb ischemia. However, limitation of EPC sources remains a major obstacle.\nDirect reprogramming has become a powerful tool to produce EPCs from fibroblasts. Some recent efforts successfully\ndirectly reprogrammed human fibroblasts into functional EPCs; however, the procedure efficacy was low. This study\ntherefore aimed to improve the efficacy of direct reprogramming of human fibroblasts to functional EPCs.\nMethods: Human fibroblasts isolated from foreskin were directly reprogrammed into EPCs by viral ETV2 transduction.\nReprogramming efficacy was improved by culturing transduced fibroblasts in hypoxia conditions (5 % oxygen).\nPhenotype analyses confirmed that single-factor ETV2 transduction successfully reprogrammed dermal fibroblasts\ninto functional EPCs.\nResults: Hypoxia treatment during the reprogramming procedure increased the efficacy of reprogramming from\n1.21 �± 0.61 % in normoxia conditions to 7.52 �± 2.31 % in hypoxia conditions. Induced EPCs in hypoxia conditions\nexhibited functional EPC phenotypes similar to those in normoxia conditions, such as expression of CD31 and\nVEGFR2, and expressed endothelial gene profiles similar to human umbilical vascular endothelial cells. These cells\nalso formed capillary-like networks in vitro.\nConclusion: Our study demonstrates a new simple method to increase the reprogramming efficacy of human\nfibroblasts to EPCs using ETV2 and hypoxia
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