Abstract：
The disruption of mitochondria homeostasis can impair the contractile function of cardiomyocytes, leading to cardiac dysfunction and an increased risk of heart failure. This study introduces a pioneering therapeutic strategy employing mitochondria derived from human umbilical cord mesenchymal stem cells (hu-MSC) (MSC-Mito) for heart failure treatment. Initially, we isolated MSC-Mito, confirming their functionality. Subsequently, we monitored the process of single mitochondria transplantation into recipient cells and observed a time-dependent uptake of mitochondria in vivo. Evidence of human-specific mitochondrial DNA (mtDNA) in murine cardiomyocytes was observed after MSC-Mito transplantation. Employing a doxorubicin (DOX)-induced heart failure model, we demonstrated that MSC-Mito transplantation could safeguard cardiac function and avert cardiomyocyte apoptosis, indicating metabolic compatibility between hu-MSC-derived mitochondria and recipient mitochondria. Finally, through RNA sequencing and validation experiments, we discovered that MSC-Mito transplantation potentially exerted cardioprotection by reinstating ATP production and curtailing AMPKα-mTOR-mediated excessive autophagy.
摘要：
线粒体稳态的破坏会损害心肌细胞的收缩功能，导致心脏功能障碍和心力衰竭风险增加。这项研究介绍了采用人脐带间充质干细胞（hu-MSC）（MSC-Mito）衍生的线粒体进行心力衰竭治疗的开创性治疗策略。最初，我们分离了MSC-Mito,确认其功能。随后，我们监测了单个线粒体移植到受体细胞的过程，并观察到体内线粒体的时间依赖性摄取。在MSC-Mito移植后观察到小鼠心肌细胞中人类特异性线粒体DNA(mtDNA)的证据。采用多柔比星（DOX）诱导的心力衰竭模型，我们证明MSC-Mito移植可以保护心脏功能，避免心肌细胞凋亡，表明hu-MSC衍生的线粒体和受体线粒体之间的代谢相容性。最后,通过RNA测序和验证实验，我们发现MSC-Mito移植可能通过恢复ATP产生和减少AMPKα-mTOR介导的过度自噬而发挥心脏保护作用.
