Niche-targeted paracrine signaling from OMSCs restores the regenerative microenvironment after SCI.

A central hurdle in spinal cord injury (SCI) therapy involves not only reconstructing neural pathways but also overcoming the detrimental inflammatory milieu. Inspired by olfactory microenvironmental niches, we implemented a niche-targeted strategy. Our investigation defines the biological properties of ectodermal olfactory mesenchymal stem cells (OMSCs) and further elucidates their niche-targeted paracrine effectin vivoandin vitro. The findings demonstrate that OMSC-conditioned medium (OMSC-CM) delivered in fibrin hydrogel mediates potent SCI repair by concurrently protecting neurons, enhancing axonal regeneration, and suppressing destructive inflammation via IL-10 signaling. Critically, persistence of IL-10 signalingin vivois sustained both by direct supply from OMSC-CM and by OMSC-CM-induced activation of CD206+macrophagesIL-10. Successful neural circuit reconstruction with OMSC-CM depends on maximizing neuronal involvement in neural pathway formation. These findings may establish a special conceptual framework for developing regenerative medicine strategies in the future.