Mitochondrial transplantation for cardiovascular diseases: opportunities and challenges—a review

Mitochondria serve as central hubs for cellular energy production, calcium homeostasis, and signal transduction, playing pivotal roles in maintaining cardiomyocyte viability and function. Mitochondrial dysfunction is closely implicated in the pathogenesis of various cardiovascular diseases, including myocardial ischemia-reperfusion injury, myocardial infarction, doxorubicin-induced cardiomyopathy, peripheral artery disease, and diabetic cardiomyopathy. Mitochondrial transplantation (MT) has emerged as a promising therapeutic strategy that involves delivering functional exogenous mitochondria to damaged tissues to restore bioenergetic capacity and promote cellular repair mechanisms. Preclinical studies across multiple animal models have demonstrated its efficacy in reducing infarct size, enhancing functional recovery, and modulating inflammatory responses. Current MT techniques encompass diverse approaches for mitochondrial isolation, storage, and delivery, with both direct injection and indirect transplantation methods under investigation. Despite encouraging results from early-phase clinical trials highlighting its safety and feasibility, significant translational challenges remain. These include unresolved mechanistic debates—such as whether benefits arise from direct mitochondrial integration or paracrine immunomodulation—as well as issues related to long-term safety, standardization of mitochondrial preparations, optimization of delivery routes, and the need for rigorous, large-scale randomized controlled trials. This review summarizes the current evidence, critically examines the opportunities and barriers in the field, and outlines key directions for future research to advance MT toward clinical application in cardiovascular medicine.