Ultrasound-guided HUC-MSCs transplantation alleviates neuropathic pain in CCI rats: a mechanistic study based on microglia/macrophage polarization and the NLRP3 inflammasome.

This study investigates the therapeutic effects of ultrasound-guided transplantation of human umbilical cord mesenchymal stem cells (HUC-MSCs) on nerve injury and neuronal recovery in chronic constriction injury (CCI) rats. Behavioral analysis showed that HUC-MSCs treatment significantly improved Paw Mechanical Withdrawal Threshold (PMWT) and Thermal Paw Withdrawal Latency (TWL), with faster recovery in the HUC-MSCs groups. Histological analysis revealed enhanced repair and regeneration, reduced inflammation, and improved results in the dual-treatment group (CCI + U2). Ultrasound and histological examination demonstrated significant nerve fiber repair, reduced inflammation, and enhanced myelin recovery, especially in the CCI + U2 group. TMT-based proteomics identified differential protein expression in the spinal dorsal horn (SDH), confirming molecular changes associated with neuronal recovery. Analysis of microglial polarization in the SDH, and macrophage polarization in the dorsal root ganglion (DRG) and sciatic nerve (SN), showed that HUC-MSCs promoted the M2 phenotype, reducing inflammation and enhancing repair. HUC-MSCs also modulated the NLRP3 inflammasome, lowering NLRP3, ASC, caspase-1, and IL-1β levels. The study further explored HUC-MSCs-derived exosomes' effects on microglial polarization and NLRP3 activity, regulated by miR-223-3p to promote anti-inflammatory and neuroprotective effects, suggesting the potential of HUC-MSCs and exosomes in nerve regeneration and neuroinflammation reduction after SN injury.