CONICET | Buscador de Institutos y Recursos Humanos

Bone marrow mononuclear cells (BMMC) include different cell types, containing a minority multipotent fraction. For this reason, BMMC have recently become a therapeutic alternative to mesenchymal stem cells, as culture is not required and phenotypic transformations can be hence avoided. Wallerian degeneration induced by nerve sectioning or compression is a simple and extremely useful experimental approach to study the pathophysiology of peripheral nervous system degenerative disorders. In this model, our group has shown systemically transplanted BMMC to spontaneously migrate to and remain in the injured nerve for as long as 60 days post injury. BMMC were also shown to enhance axonal regeneration and remyelination, and to prevent lesion-induced hyperalgesia. In this context, the aim of the present work is to evaluate whether BMMC exert their well-established beneficial effect on sciatic nerve regeneration through immunomodulatory actions. Adult C57BL/6 mice received intravenous transplantation of either BMMC or vehicle after 8-second sciatic nerve crush and were then sacrificed 1, 3 or 7 days after transplant to perform immunohistochemistry, qPCR and flow cytometry analyses. So far, immunohistochemical analyses carried out after recovery showed a small number of BMMC upregulating markers unexpressed before transplant, which led to cell phenotypic changes and transdifferentiation to Schwann cells to participate in axon ensheathment and remyelination. However, a significantly larger proportion may be speculated to have left the tissue after the inflammatory phase had finished. In addition, qPCR results have shown animals transplanted with BMMC to undergo a downregulation of pro-inflammatory signals and an upregulation of anti-inflammatory cytokines. Nevertheless, further studies are required to fully corroborate immunomodulation effects.