Neurotrophin-3 modified bone marrow mesenchymal stem cells combined with polycaprolactone scaffold can treat denervation-induced muscle atrophy in rats by regulating FasL.

We investigated the effects and mechanisms of neurotrophin-3 (NT-3)-modified bone marrow mesenchymal stem cells (BMSCs) combined with a polycaprolactone (PCL) scaffold to repair denervation-induced muscle atrophy following sciatic nerve injury (SNI) in rats. An established SNI rat model was utilized to evaluate the therapeutic efficacy of BMSCs, pcDNA3.1-NT-3, and NT-3-modified BMSCs scaffold complexes. Functional recovery of peripheral nerves was assessed through serial sciatic functional index (SFI) measurements. Histopathological analyses evaluated nerve regeneration and gastrocnemius muscle preservation, complemented by quantification of muscle wet weight and fiber cross-sectional area. Molecular mechanisms were investigated <i>via</i> RT-qPCR and Western blot to determine expression profiles of NT-3, FasL, Cleaved Caspase-3, Bcl-2, and Bax. Both individual and combined applications of BMSCs and pcDNA3.1-NT-3 composite PCL scaffolds demonstrated therapeutic efficacy in ameliorating SNI, enhancing nerve regeneration, and restoring neurological function while attenuating denervation-induced skeletal muscle atrophy. The combinatorial BMSCs/pcDNA3.1-NT-3 intervention exhibited superior neurorestorative effects through synergistic mechanisms, suggesting clinical potential for optimizing functional recovery in peripheral nerve injury (PNI) patients. Notably, SNI rats exhibited upregulated FasL expression in neuromuscular tissues, which was significantly suppressed following BMSCs/pcDNA3.1-NT-3 scaffold treatment. Lentiviral-mediated FasL overexpression (Lv-FasL) abolished the therapeutic benefits of the composite scaffold, confirming FasL's critical role in mediating these neuroprotective effects. We found out that NT-3 modified BMSCs combined with PCL scaffolds promoted nerve regeneration, repaired nerve function, and inhibited skeletal muscle atrophy in rats after sciatic nerve injury by regulating FasL expression.