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

Abstract

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 effect<i>in vivo</i>and<i>in vitro</i>. 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 signaling<i>in vivo</i>is sustained both by direct supply from OMSC-CM and by OMSC-CM-induced activation of CD206⁺macrophages^IL-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.