Mitochondria transplantation mitigates attenuation of muscle fiber regeneration by evoked contractions

Rest is generally required for full muscle regeneration after an injury; however, rehabilitative activity is often used after injury to attempt a faster recovery. While rehabilitative activity can enhance muscle regeneration, there is also a risk that returning to vigorous muscle contractions too early after sustaining an injury, could reinjure the muscle, and negatively impact full muscle regeneration. It is not known whether MT added to rehabilitative muscle activity would speed regeneration of muscle morphology more rapidly than resting during the recovery period. Therefore, submaximal electrically evoked isometric contractions (EC) were given to injured muscles of MT treated mice, to test the hypothesis that MT would attenuate the negative regenerative effects of EC and improve the restoration of muscle mass and morphology after muscle injury. Cardiotoxin (CTX) was injected into the tibialis anterior (TA) muscle of one limb of C57BL/6 mice at 8-12 weeks of age to induce muscle injury. Systemic delivery MT or PBS was administered to the mice 48 h after injury. The TA received EC at 40Hz every other day for up to 14-days after CTX injury. While EC-induced mechanical injury slowed muscle repair, muscle fiber regeneration and nuclear domain size was improved by MT. The percentage of collagen and other non-contractile tissue was elevated in CTX-injured and EC treated muscles; however, MT reduced fibrosis/non-contractile tissue deposition in regenerating muscles. Our results provide evidence that systemic mitochondria delivery can improve muscle repair and can attenuate contraction-suppressed muscle fiber regeneration during recovery after injury.