Huan Chen, Xu Chen, Zihao Zhou, Jiarong Zheng, Ye Lu, Pei Lin, Lin Ye, Yucheng Zheng, Bin Xiong, Rongwei Xu, Li Cui, Xinyuan Zhao
Mitochondrial dysfunction is a pivotal factor in the progression of various diseases, making it a critical therapeutic target. Mesenchymal stromal cells (MSCs) have shown promise in mitigating this dysfunction through the transfer of healthy mitochondria to damaged cells. This review comprehensively analyzes the mechanisms of MSC-derived mitochondrial transfer, including tunneling nanotubes (TNTs) and extracellular vesicles, and highlights their therapeutic potential across a spectrum of diseases, such as neurodegenerative disorders, ocular diseases, and inflammatory conditions. Additionally, strategies to enhance mitochondrial transfer efficiency-such as genetic modifications and optimization of MSC sources-are thoroughly explored. Despite these promising findings, challenges remain, including the need for a deeper understanding of transfer mechanisms, ensuring the quality and functionality of transferred mitochondria, and addressing potential immune responses. While MSC-derived mitochondrial transfer holds significant therapeutic potential, careful consideration of its dual nature, especially in specific pathological contexts such as cancer, is essential. With further research and technological advancements, this approach could become a cornerstone in the treatment of diseases characterized by mitochondrial dysfunction.