Recent studies have demonstrated that bone marrow mesenchymal stem cells (BMSCs) protect the injured neurons of spinal cord injury (SCI) from apoptosis while the underlying mechanism of the protective effect of BMSCs remains unclear. In this study, we found the transfer of mitochondria from BMSCs to injured motor neurons and detected the functional improvement after transplanting. Methods: Primary rat BMSCs were co-cultured with oxygen-glucose deprivation (OGD) injured VSC4.1 motor neurons or primary cortical neurons. FACS analysis was used to detect the transfer of mitochondria from BMSCs to neurons. The bioenergetics profiling of neurons was detected by Extracellular Flux Analysis. Cell viability and apoptosis were also measured. BMSCs and isolated mitochondria were transplanted into SCI rats. TdT-mediated dUTP nick end labelling staining was used to detect apoptotic neurons in the ventral horn. Immunohistochemistry and Western blotting were used to measure protein expression. Re-myelination was examined by transmission electron microscope. BBB scores were used to assess locomotor function. Results: MitoTracker-Red labelled mitochondria of BMSCs could be transferred to the OGD injured neurons. The gap junction intercellular communication (GJIC) potentiator retinoid acid increased the quantity of mitochondria transfer from BMSCs to neurons, while GJIC inhibitor 18β glycyrrhetinic acid decreased mitochondria transfer. Internalization of mitochondria improved the bioenergetics profile, decreased apoptosis and promoted cell survival in post-OGD motor neurons. Furthermore, both transplantation of mitochondria and BMSCs to the injured spinal cord improved locomotor functional recovery in SCI rats. Conclusions: To our knowledge, this is the first evidence that BMSCs protect against SCI through GJIC to transfer mitochondrial to the injured neurons. Our findings suggested a new therapy strategy of mitochondria transfer for the patients with SCI.

Damage of mitochondria in the initial period of tissue injury aggravates the severity of injury. Restoration of mitochondria dysfunction and mitochondrial-based therapeutics represent a potentially effective therapeutic strategy. Recently, mitochondrial transfer from stem cells has been demonstrated to play a significant role in rescuing injured tissues. The possible mechanisms of mitochondria released from stem cells, the pathways of mitochondria transfer between the donor stem cells and recipient cells, and the internalization of mitochondria into recipient cells are discussed. Moreover, a novel strategy for tissue injury based on the concept of stem cell-derived mitochondrial transplantation is pointed out, and the advantages and challenges are summarized.

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The integration of mesenchymal stem cell sheet and bFGF-loaded fibrin gel in knitted PLGA scaffolds synergistically promoted rat At regeneration