Mitochondrial transfer from adipose-derived stem cells reprograms macrophage lipid metabolism to improve fat graft survival

Autologous fat grafting is common for soft tissue repair, but often results in adipocyte necrosis due to ischaemia and hypoxia, causing inflammation and poor graft retention. Our research indicates that adipose-derived mesenchymal stem cells (ASCs) induce mitochondrial fatty acid β-oxidation (FAO) in macrophages, thus facilitating their M2 polarization and ultimately enhancing graft survival. ASCs also transfer mitochondria to recipient cells by tunnelling nanotubes (TNTs), increasing energy metabolism and the oxidative stress response. On the basis of these findings, we propose that ASCs facilitate mitochondrial transfer to macrophages through TNTs, which in turn enhances FAO, thus promoting M2 polarization and ultimately improving fat graft retention. This study established a model of ASCs-assisted fat grafting in mice and an in vitro coculture system comprising ASCs and high-fat-treated macrophages. ASCs were treated with the actin polymerization inhibitor latrunculin A (latA) to block TNTs formation. We evaluated lipid deposition, mitochondrial transfer in macrophages, and mitochondrial function using electron microscopy, immunofluorescence, and qPCR. The findings indicated that ASCs enhance FAO in macrophages and improve fat graft retention, but latA pretreatment inhibited mitochondrial transfer, decreasing these effects. This research reveals a mechanism through which ASCs influence macrophage lipid metabolism through TNTs-mediated mitochondrial transfer, providing insights for enhancing fat graft survival.