Adult bone marrow mesenchymal and neural crest stem cells are chemoattractive and accelerate motor recovery in a mouse model of spinal cord injury

Abstract

Introduction: Stem cells from adult tissues were considered for a long time as promising tools for regenerative therapy of neurological diseases, including spinal cord injuries (SCI). Indeed, mesenchymal (MSCs) and neural crest stem cells (NCSCs) together constitute the bone marrow stromal stem cells (BMSCs) that were used as therapeutic options in various models of experimental SCI. However, as clinical approaches remained disappointing, we thought that reducing BMSC heterogeneity should be a potential way to improve treatment efficiency and reproducibility. Methods: We investigated the impact of pure populations of MSCs and NCSCs isolated from adult bone marrow in a mouse model of spinal cord injury. We then analyzed the secretome of both MSCs and NCSCs, and its effect on macrophage migration in vitro. Results: We first observed that both cell types induced motor recovery in mice, and modified the inflammatory reaction in the lesion site. We also demonstrated that NCSCs but especially MSCs were able to secrete chemokines and attract macrophages in vitro. Finally, it appears that MSC injection in the spinal cord enhance early inflammatory events in the blood and spinal cord of SCI mice. Conclusions: Altogether, our results suggest that both cell types have beneficial effects in experimental SCI, and that further investigation should be dedicated to the regulation of the inflammatory reaction following SCI, in the context of stem cell-based therapy but also in the early-phase clinical management of SCI patients.