Allogeneic adipose ‐derived stem cells promote ischemic muscle repair by inducing M2 macrophage polarization via the HIF‐1α/IL‐10 pathway

This study investigated the immunomodulatory effect of ASCs on ischemic muscle repair and explored the specific mechanism. We found that the ability of RAW264.7 cells to migrate was impaired in hypoxia, whereas coculturing with ASCs could enhance the migration capac ity. In addition, under hypoxic conditions, the paracrine effect of ASCs was enhanced and ASCs could induce RAW264.7 macrophages towards the anti‐inflammatory M2 phenotype. We further demonstrated that ASCs‐derived interleukin 10 (IL‐10), mediated by hypoxia inducible factor‐1α (HIF‐1α), played a crucial role in the induction of M2 macrophages by activating the signal transducer and activator of transcription 3 (STAT3) /Arginase (Arg‐1) pathway. Our in vivo experiments revealed that transplanted ASCs exhibited an immunomodulatory effect by recruiting macrophages to ischemic muscl e and increasing the density of M2 macrophages. The transplantation of ASCs into ischemic limbs induced increased blood flow reperfusion and limb salvage rate, whereas the depletion of tissue macrophages or transplanting HIF‐1α‐silenced ASCs inhibited the therapeutic effect. These findings eluc idated the critical role of macrophages in ASCs‐mediated ischemic muscle repair and proved that allogeneic ASCs could exert the protective effect by enhancing the recruitment of macrophages and inducing macrophages towards M2 phenotype through HIF‐1α/IL‐10 pathway.© AlphaMed Press 2020Significance StatementThis study focu...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Regenerative Medicine Source Type: research