Mitochondrial Transplantation/Transfer: Promising Therapeutic Strategies for Spinal Cord Injury.

Spinal cord injury (SCI) remains an unresolved and complex medical challenge. In SCI, mitochondrial dysfunction leads to calcium overload and an increase in reactive oxygen species (ROS). Intercellular mitochondrial transfer has the potential to rescue surviving neurons, while exogenous mitochondrial transplantation can be performed through direct injection or cell-assisted methods. This review explored the current state of research on mitochondrial transplantation and transfer as potential treatments for SCI. It also analyzed the therapeutic implications, influencing factors, and advanced delivery methods for both endogenous mitochondrial transfer and exogenous mitochondrial transplantation. Furthermore, future research directions, including optimizing mitochondrial delivery methods, determining optimal dosages for different delivery approaches, were discussed based on larger animal models and clinical trials. The goal of this review was to introduce novel concepts and prospects for SCI therapy and to contribute to the advancement of medical research in this field. The Translational Potential of This Article: At present, SCI lacks effective therapies, with mitochondrial dysfunction playing a central role in neuronal damage. Mitochondrial transplantation holds promise for restoring bioenergetic function. However, key challenges remain, including optimizing delivery methods, determining appropriate dosages, scalability, donor mitochondrial sourcing, regulatory hurdles and ensuring successful integration. Addressing these issues requires non-invasive platforms, validation in large-animal models, and clinical trials. This approach may bridge mitochondrial biology with translational engineering, thereby advancing the development of regenerative therapies for SCI.