Peripheral Nerve Regeneration Using a Cytokine Cocktail Secreted by Skeletal Muscle-Derived Stem Cells in a Mouse Model

Severe peripheral nerve injury, which does not promise natural healing, inevitably requires clinical treatment. Here, we demonstrated the facilitation effect of peripheral nerve regeneration using a cytokine cocktail secreted by skeletal muscle-derived stem cells (Sk-MSCs). Mouse sciatic nerve was transected with a 6 mm gap and bridged collagen tube, and the culture supernatant of Sk-MSCs with 20% adult mouse serum (AMS)/Iscove's modified Dulbecco's medium (IMDM) was administered into the tube immediately after the operation, followed by an injection once a week for six weeks through the skin to the surrounding tube of the cytokine (CT) group. Similarly, 20% AMS/IMDM without cytokines was administered to the non-cytokine control (NT) group. Tension recovery in the plantar flexor muscles via electrical stimulation at the upper portion of the damaged nerve site, as well as the numerical recovery of axons and myelinated fibers at the damaged site, were evaluated as an index of nerve regeneration. Specific cytokines secreted by Sk-MSCs were compared with damaged sciatic nerve-derived cytokines. Six weeks after operation, significantly higher tension output and numerical recovery of the axon and myelinated fibers were consistently observed in the CT group, showing that the present cytokine cocktail may be a useful nerve regeneration acceleration agent. We also determined 17 candidate factors, which are likely included in the cocktail.