Substance P modulates biological essential characteristics of bone marrow-derived stromal progenitor cells in vivo and in vitro
Maria Jose Dubon Medina
Substance P Bone Marrow-Derived Stromal Cells;
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Bone marrow derived mesenchymal stem cells (MSCs) are currently one of the most popular cells being tested for the development of stem cell therapies for the treatment of several conditions. MSCs have been found to be able to mobilize from the bone marrow (BM) to peripheral tissues. This allows MSCs to contribute in the process of wound healing by different strategies such as the immunomodulation of immune cells and the direct contribution to tissue repair through their ability to secrete cytokines and to differentiate into various cell types. Cell-cell adhesion molecules such as N-cadherin are thought to be involved in the mobilization of MSCs along with the participation of other factors. Among these factors is SDF-1, a cytokine expressed by MSCs which participates in the trafficking of both hematopoietic stem cells (HSCs) and MSCs between the BM and the periphery. Previous studies demonstrated that substance P (SP), a neurotransmitter involved in pain perception, induces the proliferation of MSCs in vitro, and suggested the involvement of the ERK1/2 and the TCF/LEF-β-catenin pathways as part of the mechanism. Furthermore, they showed that SP enhances the migration of MSCs from the BM to injury sites to promote healing. In this study we found that SP increases the CFU-F, the osteogenic differentiation potential and the mRNA levels of SDF-1 and N-cadherin of the bone marrow total cells. We also observed an increase in the proliferation of the stromal cell line OP9 and in the levels of cyclin D1 in response to SP treatment. However, SP did not induced the activation of the ERK1/2 and the TCF/LEF-β-catenin pathways in OP9 cells. Moreover, we found that SP induces the migration of another stromal cell line, ST2. Overall, this study suggests that SP has the ability to modulate certain properties of MSCs linked to their therapeutic potential and their role in stem cell trafficking. Yet, the mechanisms involved in the SP-mediated proliferation and mobilization of MSCs remain unknown.