Abstract :
[en] Spinal cord injury (SCI) treatment represents a critical issue in clinical research and patient care. Stem cell-based replacement therapies have already been proposed worldwide, especially studying stem cells from the adult bone marrow stroma. Previous studies focusing on those cells did not specifically consider their intrinsic embryonic heterogeneity, thus intermingling different stem cells subpopulations to treat experimental SCI or even injured patients.
In this study, we decided to compare adult bone marrow neural crest-derived stem cells (NCSC) and mesenchymal stem cells (MSC), and highlight which of their specific properties could be relevant in therapeutic perspectives. In that purpose, we compared NCSC and MSC isolated from adult mouse bone marrow. We then compared the effects that both cell types could exert once grafted inside an injured spinal cord. Cells were injected into the spinal cord of mice that right after a spinal cord contusion at the T11-12 spinal level. Our results indicate that both MSC and NCSC-injected mice recovered locomotion abilities faster than control mice (as assessed by BMS scoring). Additionally, we observed that after 28 days post-injury, the lesion volume tended to decrease in mice that received cell graft compared to control group. Interestingly, it appeared that MSC seemed to be able to modulate inflammation inside the lesion, more than NCSC. Indeed, MSC-graft increased early neutrophil and macrophage recruitment in the bloodstream and inside the spinal cord, and increased the number of arginase-1-expressing cells remaining in the spinal cord after 28 days. In parallel, we compared the secretome of both NCSC and MSC, and noticed some interesting differences: MSC secreted several chemokines reflecting possible immunomodulating properties, while NCSC secreted products might be able to enhance neurite outgrowth. Indeed, preliminary data showed that NCSC induced neuritogenesis on primary neurons in vitro. Altogether, those results should help to improve and optimize cell-based therapies parameters and/or to define precise and efficient pharmacological treatments for SCI patients.