Cdc42-Modified BMSC-Derived exosomes promote acellular nerve allografts to bridge sciatic nerve defects.

Abstract

Peripheral nerve injury (PNI) often results in persistent functional deficits, and current treatments remain suboptimal. This study developed a tissue-engineered graft by integrating Cdc42-modified bone marrow-derived mesenchymal stem cell (BMSC)-derived exosomes (Exos-Cdc42) with an acellular nerve allograft (ANA) and evaluated its therapeutic potential for nerve regeneration and functional recovery. Exosomes were isolated from BMSCs, and Exos-Cdc42 were generated by transfecting these cells with Cdc42 overexpression vectors. In vitro, Exos-Cdc42 significantly enhanced Schwann cell proliferation, migration, and secretion of neurotrophic factor (BDNF, NGF, CNTF), while upregulating repair-associated markers and downregulating myelination-related markers. In vivo, the combination of Exos-Cdc42 and ANA improved functional recovery of the sciatic nerve, as evidenced by higher sciatic functional index scores and increased muscle weight. Histological analyses demonstrated enhanced axonal regeneration and myelination, characterized by thicker myelin sheaths and larger axon diameters. These findings suggest that Exos-Cdc42 enhance the therapeutic efficacy of ANA by promoting Schwann cell-mediated repair responses, representing a promising strategy for peripheral nerve regeneration.