ABSTRACT
Hybrid transplantation of skeletal muscle-derived multipotent stem cells (Sk-MSCs) and bioabsorbable polyglyconate (PGA) felt was studied as a novel regeneration therapy for the transected recurrent laryngeal nerve (RLN). Sk-MSCs were isolated from green fluorescence protein transgenic mice and then expanded and transplanted with PGA felt for the hybrid transplantation (HY group) into the RLN transected mouse model. Transplantation of culture medium (M group) and PGA + medium (PGA group) were examined as controls. After eight weeks, trans-oral video laryngoscopy demonstrated 80% recovery of spontaneous vocal-fold movement during breathing in the HY group, whereas the M and PGA groups showed wholly no recoveries. The Sk-MSCs showed active engraftment confined to the damaged RLN portion, representing favorable prevention of cell diffusion on PGA, with an enhanced expression of nerve growth factor mRNAs. Axonal re-connection in the HY group was confirmed by histological serial sections. Immunohistochemical analysis revealed the differentiation of Sk-MSCs into Schwann cells and perineurial/endoneurial cells and axonal growth supportive of perineurium/endoneurium. The number of axons recovered was over 86%. These results showed that the stem cell and cytokine delivery system using hybrid transplantation of Sk-MSCs/PGA-felt is a potentially practical and useful approach for the recovery of transected RLN.
ABSTRACT
The therapeutic effects of voluntary exercise on the recovery of long-gap nerve injury following the bridging of an acellular conduit filled with human skeletal muscle-derived stem cells (Sk-SCs) have been described. Human Sk-SCs were sorted as CD34âº/45- (Sk-34) cells, then cultured/expanded under optimal conditions for 2 weeks. Surgery to generate a long-gap sciatic nerve injury was performed in athymic nude mice, after which the mice were divided into exercise (E) and non-exercise (NE) groups. The mice were housed in standard individual cages, and voluntary exercise wheels were introduced to the cages of the E group one week after surgery. After 8 weeks, the human Sk-34 cells were actively engrafted, and showed differentiation into Schwann cells and perineurial cells, in both groups. The recovery in the number of axons and myelin in the conduit and downstream tibial nerve branches, and the lower hindlimb muscle mass and their tension output, was consistently higher by 15-25% in the E group. Moreover, a significantly higher innervation ratio of muscle spindles, reduced pathological muscle fiber area, and acceleration of blood vessel formation in the conduit were each observed in the E group. These results showed that the combined therapy of tube-bridging, Sk-34 cell transplantation, and voluntary exercise is a potentially practical approach for recovery following long-gap nerve injury.
