Adult rat mesenchymal stem cells delay denervated muscle atrophy.

Abstract

To evaluate the function of rat mesenchymal stem cells (rMSCs) on denervated gastrocnemius muscles and to address the role of ciliary neurotrophic factor (CNTF) in rMSCs, denervated Wistar rats were separately injected with culture media (sham control), CNTF protein, 2.5 × 10(5) siCNTF-treated rMSCs, 2.5 × 10(5) GFP-transfected rMSCs, or 2.5 × 10(5) untreated rMSCs. Muscle function was assessed at different time points post-surgery. Tibial nerve and gastrocnemius muscle samples were taken at 4, 8, and 12 weeks for histochemistry, and neuromuscular junction repair was also examined by electron microscopy. Fluorescence immunocytochemistry on tissue sections confirmed neurotrophin expression in rMSCs but with little evidence of neuronal differentiation. The engraftment of rMSCs significantly preserved the function of denervated gastrocnemius muscle based both on evaluation of muscle function and direct examination of muscle tissue. Further, the density and depth of the junctional folds were visibly reduced 12 weeks after surgery and transplantation, especially in control group. Knockdown of CNTF expression in rMSCs failed to block muscle preservation, although administration of CNTF protein alone inhibited muscle atrophy, which indicating that delivery of rMSCs could preserve gastrocnemius muscle function following denervation and post-junctional mechanisms involved in the repairing capability of rMSCs.