CONICET | Buscador de Institutos y Recursos Humanos

Regenerative action and immune modulation of bone marrow cell transplant in sciatic nerve injuryGonzalo Piñero; Marianela Vence; Vanina Usach; Paula A. Soto and Patricia Setton-Avruj.Wallerian degeneration induced by nerve ligation, sectioning or compression is a simple and extremely useful experimental approach to study the pathophysiology of peripheral nervous system degenerative-regenerative process. Our group has shown systemically transplanted bone marrow mononuclear cells (BMMC) to spontaneously migrate to and remain in the crush-injured nerve for as long as 60 days post injury. BMMC were also shown to enhance axonal regeneration and remyelination, promote functional recovery and to prevent lesion-induced hyperalgesia.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 this context, the aim of the present work is to evaluate whether bone marrow cell transplant exert their well-established beneficial effect on sciatic nerve regeneration through immunomodulatory actions.Adult C57BL/6 mice received intravenous bone marrow cell transplantation or vehicle after 8-second sciatic nerve crush and were then sacrificed to perform immunohistochemistry, ELISA, qPCR and flow cytometry analyses. In addition, walking track and hot plate test were done at intermediate time points. So far, mice model resemble results obtained in rats in terms of remyelination effect. More interesting, transplanted animals apparently undergo a downregulation of pro-inflammatory signals and an upregulation of anti-inflammatory cytokines. Nevertheless, further studies are required to fully corroborate immunomodulation effects.