FNDC5-overexpressed BMSCs Attenuated Brachial Plexus Root Avulsion by Enhancing BMSCs Survival and Inhibiting Motoneurons Apoptosis

<h2>Abstract</h2><h3>Background</h3> Brachial plexus root avulsion (BPRA) causes severe motor function impairment. Inhibition of spinal motoneuron (MN) apoptosis is crucial for BPRA treatment. This study explores the mechanisms by which Fibronectin Type III Domain Containing 5 (FNDC5)-modified bone marrow mesenchymal stem cells (FNDC5/BMSCs) attenuate BPRA. <h3>Methods</h3> BMSCs were transduced with FNDC5, and their anti-apoptotic effects under hypoxia were evaluated. Exosomes (hereinafter referred to as exos) were extracted and characterized. The biological functions of NSC34 cells were assessed using CCK-8 and flow cytometry. FNDC5-overexpressed BMSCs were transplanted into BPRA mice to evaluate therapeutic effects. <h3>Results</h3> FNDC5 overexpression significantly enhanced BMSC viability and reduced hypoxia-induced apoptosis. FNDC5/BMSCs exhibited decreased levels of cleaved caspase-3 and Bax, while Bcl-2 expression increased. FNDC5 was efficiently transferred into exosomes, which attenuated NSC34 cell apoptosis and regulated BDNF expression. <i>In vivo</i>, FNDC5/BMSCs improved forelimb motor function, reduced MN apoptosis, and increased MN axon numbers. <h3>Conclusion</h3> FNDC5-engineered BMSCs promote BPRA recovery by enhancing BMSC survival and inhibiting MN apoptosis, suggesting a potential therapeutic strategy for BPRA.