Transplantation of thermosensitive hydrogel encapsulated miR-216a-5p overexpressing mesenchymal stem cells for functional recovery of spinal cord injury

Spinal cord injury (SCI) is one of the most incapacitating conditions, with neuropathic pain (NP) as a comorbidity that is the most difficult to treatment. In recent years, microRNAs (miRNAs) have been studied more thoroughly in SCI. In this study, based on the construction of the SCI rat model, miR-216a-5p expression was reduced in SCI rats through experimental validation analysis. And human mesenchymal stem cells (hMSCs) overexpressing miR-216a-5p were loaded by constructing thermosensitive hydrogels and transplanted into SCI rats. It was found that the constructed hydrogel system exhibited temperature-dependent phase change behavior and biodegradability, and rats with spinal cord injury showed considerable behavioral recovery and significantly reduced cellular mortality after transplantation. Mechanistic studies revealed that sustained release of miR-216a-5p was able to bind to the 3'UTR of NUDT21 and involve in the regulation of recovery after SCI through modulation of NUDT21, thus greatly increasing recovery after spinal cord injury. Thus, thermosensitive hydrogel-encapsulated human mesenchymal stem cells overexpressing miR-216a-5p provide a microenvironmentally responsive and noninvasive pathway for recovery from spinal cord injury, we hypothesized that miR-216a-5p could be a potential biomarker for neuropathic pain.