Human Menstrual Blood–Derived Endometrial Stem Cells Promote Functional Recovery by Improving the Inflammatory Microenvironment in a Mouse Spinal Cord Injury Model

Abstract

Spinal cord injury (SCI) is a traumatic injury of the central nervous system. Because neurons are damaged and difficult to regenerate after SCI, its repair remains challenging. However, recent research on stem cell therapy have favored its use after SCI. In this study, based on the establishment of a mouse SCI model, human menstrual blood–derived endometrial stem cells (MenSCs) were intrathecally injected to explore the role and molecular mechanism of MenSCs in SCI. MenSCs were transplanted following SCI in the animal model, and behavioral evaluations showed that MenSC transplantation improved functional recovery. Therefore, samples were collected after 7 days, and transcriptome sequencing was performed. Gene Ontology (GO) enrichment analysis revealed that SCI is closely related to immune system processes. After transplantation of MenSCs, the immune response was significantly activated. In the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, MenSC transplantation was found to be closely related to Th1, Th2, and Th17 cell differentiation pathways. Neuronal damage and glial cell proliferation and activation in the different groups were detected by fluorescence immunohistochemistry and Western blotting 7 days after SCI. Simultaneously, the activation of different types of microglia was detected and the expression of pro-inflammatory and anti-inflammatory factors was quantitatively analyzed. The results showed that MenSC transplantation and sonic hedgehog (Shh)–induced MenSCs accelerated neuronal recovery at the injured site, inhibited the formation of glial cells and microglial activation at the injured site, inhibited the expression of inflammatory factors, and improved the inflammatory microenvironment to achieve functional recovery of SCI. This study provides an experimental basis for the study of the role and molecular mechanism of MenSCs in SCI repair, and a reference for the role of Shh-induced MenSCs in SCI repair.