HUCMSCs transplantation combined with ultrashort wave therapy attenuates neuroinflammation in spinal cord injury through NUR77/ NF-κB pathway

Abstract Aims Spinal cord injury (SCI) is a major cause of long-term physical impairment. Currently, treatment for SCI is limited to supportive measures, which can lead to permanent disability, representing a serious social burden. The present study aimed to evaluate the inflammatory microenvironment effects of human umbilical cord mesenchymal stem cells (HUCMSCs)+ Ultrashort Wave (USW) therapy on SCI and reveal possible mechanisms. Main methods Low-dose USW was treated one day after SCI, and HUCMSCs suspension was transferred to the lesion using a micro-syringe 7 days after SCI. The functional effects of HUCMSCs and USW, separately and combinedly, were measured, together with the infiltration of CD3+ cells, formation of A1 astrocytes and activation of NUR77/ NF-κB pathway. Key findings Our results showed that HUCMSCs+USW therapy improved motor function of SCI rat, together with decreased infiltration of CD3+ T cells, and decreased induction of microglia and A1 astrocytes. And also USW treatment played a very important role on decreasing the infiltration of CD3+ T cells and IBA-1+ cells. Reduced production of pro-inflammatory cytokines IL-1β and IL-6 was also observed in rats receiving HUCMSCs+USW therapy, medicated by NUR77/NF-κB pathway. Significance These findings indicated that HUCMSCs+USW therapy could attenuate inflammatory microenvironment through NUR77/NF-κB signaling pathway, which might contribute to its better outcome.