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

MSCs transfered mitochondria to M φ, which elicited Mφ into anti-inflammatory phenotype and ameliorated kidney injury through activation of PGC-1α. AbstractMesenchymal stem cells (MSCs) have fueled ample translation for treatment of immune-mediated diseases. Our previous study had demonstrated that MSCs could elicit macrophages (M φ) into anti-inflammatory phenotypes, and alleviate kidney injury in diabetic nephropathy (DN) mice via improving mitochondrial function of Mφ, yet the specific mechanism was unclear. Recent evidence indicated that MSCs communicated with their microenvironment through exchanges of mitochondria. By a coculture 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 polarization. Furthermore, we found that MSCs-Mito transfer activated peroxisome proliferator-activat ed receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis. In addition, PGC-1α interacted with TFEB in high glucose-induced Mφ, leading to the elevated lysosome-autophagy, which was essential to removal of damaged mitochondria. As a result, in Mφ, the mitochondrial bioener gy 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 importantly, MSCs-Mito transfer could be observed in DN mice, and the adoptive transfer o...
Source: Stem Cells - Category: Stem Cells Authors: Tags: REGENERATIVE MEDICINE Source Type: research