Mitochondrial Transplantation Therapy for Ischemic Stroke: Progress and Challenges

Ischemic stroke is characterized by high morbidity, high disability, high mortality, high recurrence and high economic burden, which remains second leading cause of death and the third leading cause of disability worldwide. Although continuous progress has been made in vascular recanalization therapy and pharmacological treatment, the effect of these treatments for ischemic stroke has not yet met the expectations of patients and their families. Current clinical therapeutic regimens focus primarily on revascularization and antithrombotic, while neuroprotective strategies are still notably lacking. The main purpose of acute ischemic stroke treatment is to rescue neurons in ischemic penumbra, but high-energy-consuming neurons are highly sensitive and vulnerable to ischemia-hypoxia due to cessation of cerebral blood flow. Mitochondria damage and dysfunction is one of the most critical pathological consequences of hypoxia, as well as a significant contributor to neuronal death. Emerging evidence have demonstrated that mitochondria-targeted strategy is promising for treatment of ischemic stroke, and drugs such as butylphthalide and edaravone have been demonstrated to restore mitochondrial function. However, sustained ischemic-hypoxia often leads to irreversible mitochondrial damage in acute phase of cerebral ischemia. Therefore, mitochondrial transplantation or replacement might be an alternative and effective strategy for treatment of ischemic stroke, especially in acute phase. Although evidence from animal studies have shown that mitochondrial transplantation could improve energy metabolism and prevent cell death, clinical studies have not demonstrated its therapeutic efficacy in practice, highlighting the need for in-depth investigation into mitochondrial transplantation. This article reviews the advances and limitations in therapeutic role and mechanisms of mitochondrial transplantation therapy for ischemic stroke, and discusses the challenges in its translational and clinical application.