Mitochondrial transfer from MSCs to macrophages restricts inflammation and alleviates kidney injury in diabetic nephropathy mice via PGC ‐1α activation

AbstractMesenchymal stem cells (MSCs) have fueled ample translation for treatment of immune ‐mediated diseases. Our previous study had demonstrated that MSCs could elicit macrophages (Mϕ) into anti‐inflammatory phenotypes, and alleviate kidney injury in diabetic nephropathy mice via improving mitochondrial function of Mϕ, yet the specific mechanism was unclear. Recent evidence indica ted that MSCs communicated with their microenvironment through exchanges of mitochondria. By a co‐culture system consisting of MSCs and Mϕ, we showed that MSCs‐derived mitochondria (MSCs‐Mito) were transferred into Mϕ, and the mitochondrial functions were improved, which contributed to M2 po larization. Furthermore, we found that MSCs‐Mito transfer activated peroxisome proliferator‐activated receptor gamma coactivator‐1 alpha (PGC‐1α)‐mediated mitochondrial biogenesis. In addition, PGC‐1α interacted with TFEB in high glucose (HG)‐induced Mϕ, leading to the elevated lyso some‐autophagy, which was essential to removal of damaged mitochondria. As a result, in Mϕ the mitochondrial bioenergy and capacity to combat inflammatory response were enhanced. Whereas, the immune‐regulatory activity of MSCs‐Mito was significantly blocked in PGC‐1α knockdown Mϕ. More im portantly, MSCs‐Mito transfer could be observed in DN mice, and the adoptive transfer of MSCs‐Mito educated Mϕ (MϕMito) inhibited the inflammatory response and alleviated kidney injury. While the ki...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Regenerative Medicine Source Type: research