摘要：

Background & Aim Mesenchymal stromal cells (MSCs) are considered to be a promising cellular therapy in various human pathologies. Despite numerous studies indicating the efficacy of MSCs in ischemic animal models, clinical trials reported controversial outcomes. Oxygen concentration in culture condition is considered to be a key factor and displays a variety of therapeutically relevant effects. Since our current knowledge on MSC expanded under hypoxic conditions is very limited, we aimed to characterize the mechanism from normoxic vs. hypoxic conditions in limb ischemic model. Methods, Results & Conclusion Umbilical cord-derived MSCs were grown under normoxic and hypoxic conditions, and hTERT was transfected to havvest single cell-derived colonies. Colonies with different angiogensis potential were applied for transcriptom and protenomic assay. Gremlin1 was found to highly corelated to angiogensis. Therefore, the knock-in and knock-down of Gremlin1 in MSCs were uesd for limb ischemic animal model to evaluate the therapeutic capabilty. The mice with highly Gremlin1 MSCs transplanted were significat protected by counterpart. This study demonstrates that overexpression of GREM1 in hypoxia-expanded MSCs have greater therapeutic effects against ischemia compared with normoxic MSCs by enhancing the angiogensis, which may provide new tools for studies investigating the treatment of ischemic diseases.

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