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

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-kappa B 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-1 beta and IL-6 was also observed in rats receiving HUCMSCs+USW therapy, medicated by NUR77/NF-kappa B pathway. Significance: These findings indicated that HUCMSCs+USW therapy could attenuate inflammatory microenvironment through NIJR77/NF-kappa B signaling pathway, which might contribute to its better outcome.