Testosterone propionate can promote effects of acellular nerve allograft‐seeded bone marrow mesenchymal stem cells on repairing canine sciatic nerve

Abstract

Peripheral human nerves fail to regenerate across long tube implants (>2cm), and tissue-engineered nerve grafts represent a promising treatment alternative. The present study aims to investigate the testosterone propionate (TP) repair effect of acellular nerve allograft (ANA) seeded with allogeneic bone marrow mesenchymal stem cells (BMSCs) on 3-cm canine sciatic nerve defect. ANA cellularized with allogeneic BMSCs was implanted to the defect, and TP was injected into the lateral crus of the defected leg. The normal group, the autograft group, the ANA+BMSCs group, the ANA group, and the nongrafted group were used as control. Five months postoperatively, dogs in the TP+ANA+BMSCs group were capable of load bearing, normal walking, and skipping, the autograft group and the ANA+BMSCs group demonstrated nearly the same despite a slight limp. The compound muscle action potentials (CMAPs) on the injured side to the uninjured site in the TP+ANA+BMSCs group were significantly higher than that in the ANA+BMSCs group [CMAPs ratio at A: F(3, 20)=191.40; 0.02, CMAPs ratio at B: F(3, 20)=43.27; 0.01]. Masson trichrome staining revealed that in the TP+ANA+BMSCs group, both the diameter ratio of the myelinated nerve and the thickness ratio of regenerated myelin sheath were significantly larger than that in the other groups [the diameter of myelinated nerve fibers: F(3, 56)=13.45; P<.01, the thickness ratio of regenerated myelin sheath: F(3, 56)=51.25; P<.01]. In conclusion, TP could significantly increase the repairing effects of the ANA+BMSCs group, and their combination was able to repair 3-cm canine sciatic nerve defect. It therefore represents a promising therapeutic approach.