Mesenchymal Stromal Cell Mitochondrial Transfer as a Cell Rescue Strategy in Regenerative Medicine: A Review of Evidence in Preclinical Models.

Mesenchymal stromal cells (MSC) have excellent clinical potential and numerous properties that ease its clinical translation. Mitochondria play a crucial role in energy metabolism, essential for cellular activities, such as proliferation, differentiation, and migration. However, mitochondrial dysfunction can occur due to diseases and pathological conditions. Research on mitochondrial transfer from MSCs to recipient cells has gained prominence. Numerous studies have demonstrated that mitochondrial transfer led to increased adenosine triphosphate (ATP) production, recovered mitochondrial bioenergetics, and rescued injured cells from apoptosis. However, the complex mechanisms that lead to mitochondrial transfer from healthy MSCs to damaged cells remain under investigation, and the factors contributing to mitochondrial bioenergetics recovery in recipient cells remain largely ambiguous. Therefore, this review demonstrates an overview of recent findings in preclinical studies reporting MSC mitochondrial transfer, comprised of information on cell sources, recipient cells, dosage, route of administration, mechanism of transfer, pathological conditions, and therapeutic effects. Further to the above, this research discusses the potential challenges of this therapy in its clinical settings and suggestions to overcome its challenges.