Mitochondrial uptake and translocation by macrophages promotes vascular regeneration in peripheral ischemia

Mitochondrial transplantation promotes cardiac repair following injury; however, its effects on limb ischemia due to peripheral artery disease (PAD) remain unclear. In this study, transplantation with mitochondria isolated from both murine muscle tissue and human arterial blood significantly promotes revascularization and blood flow recovery in a hindlimb ischemia mouse model. Our findings further show that transplanted mitochondria promote macrophages infiltrating into ischemic regions. Additionally, internalization of the mitochondria promotes macrophage M2-like polarization, resulting in increased pro-angiogenic factors expression and secretion and subsequent endothelial cell and smooth muscle cell proliferation. In conclusion, mitochondrial transplantation shows considerable potential in improving peripheral ischemia and provides therapeutic options for patients with PAD.