Transplantation of encapsulated mitochondria alleviates dysfunction in mitochondrial and Parkinson's disease models.
Shiwei Du, Qi Long, Yanshuang Zhou, Jiangqin Fu, Hao Wu, Liang Yang, Yaohang Xie, Yingzhe Ding, Maolei Zhang, Jingyi Guo, Mengfei Wang, Jiajun Lin, Mingli Hu, Jian Zhang, Deyang Yao, Wei Li, Feixiang Bao, Ge Xiang, Yi Wu, Yile Huang, Haozhao Liang, Rui Wang, Heying Li, Baodan Chen, Chong Li, Junwei Wang, Jiwei Zhang, Dajiang Qin, Jianwei Sun, Yun Zhu, Fei Sun, Wuming Wang, Gang Lu, Wai-Yee Chan, Hui Zhao, Chenli Liu, Xingguo Liu
Abstract
Mitochondrial transplantation holds significant potential for the treatment of mitochondrial diseases. However, how to efficiently deliver exogenous mitochondria to somatic cells or tissues remains unresolved. We present a mitochondrial transplantation approach to deliver mitochondria into the cells and tissues of mice and monkeys with high efficiency, based on encapsulating mitochondria with vesicles derived from the plasma membrane of erythrocytes. Treatment with encapsulated mitochondria complemented the loss, deletion, or mutation of mitochondrial DNA, thereby rescuing the associated bioenergetic and biochemical defects in patient-derived cells with mitochondrial disorders. Furthermore, mitochondrial capsules rescued the mitochondrial DNA depletion syndrome and Leigh syndrome in Dguok-/- and Ndufs4-/- mouse models, respectively. Moreover, in a mouse model of Parkinson's disease, mitochondrial capsules rescued neuron loss, improved motor skills, and restored mitochondrial function in the affected brain regions. Our study demonstrates the potential of this mitochondrial capsule as a treatment for mitochondrial disorders and proposes an "organelle therapy" strategy in regenerative medicine.