Hepatocyte growth factor-overexpressing bone marrow stem cells relieve incision-induced postoperative pain

Bone marrow-derived mesenchymal stem cells (BMSCs) have demonstrated therapeutic promise for tissue repair, owing to their multipotent differentiation and immunomodulatory properties. However, their therapeutic efficacy is frequently constrained by poor survival and inadequate integration into damaged tissues. Hepatocyte growth factor (HGF) is a potent cytokine that promotes cell survival, angiogenesis, and anti-inflammatory responses. This study aimed to evaluate the therapeutic potential of HGF-overexpressing BMSCs in a rat model of postoperative pain, specifically examining their effects on pain alleviation, inflammatory modulation, and tissue repair. Human BMSCs were transduced with a recombinant adeno-associated virus encoding human HGF (rAAV-HGF) and confirmed for osteogenic and adipogenic differentiation. Adult Sprague Dawley rats underwent gracilis muscle incision to induce postoperative pain and were treated with either BMSCs or HGF-overexpressing BMSCs via intrathecal injection. Pain behaviors were assessed over 21 days, and tissue samples were analyzed by RT-qPCR, ELISA, and Western blot to evaluate inflammation, microglial polarization, and fibrosis. HGF-overexpressing BMSCs secreted significantly higher levels of HGF without impairing their differentiation potential. In vivo, these cells significantly reduced mechanical allodynia and thermal hyperalgesia, promoted anti-inflammatory microglial polarization, reduced pro-inflammatory cytokines (IL-1β, TNF-α), and decreased fibrosis markers (Collagen I, α-SMA), while increasing anti-inflammatory IL-10. In conclusion, HGF-overexpressing BMSCs significantly enhance the analgesic, anti-inflammatory, and anti-fibrotic effects of conventional BMSC therapy, providing a promising approach for managing postoperative pain and promoting tissue repair.