SETTON Clara Patricia
congresos y reuniones científicas
Migration of bone marrow mononuclear cells to the crushed sciatic nerve: Its effect on remyelination.
Chicago, Estados Unidos de Norteamérica.
Congreso; 39th annual meeting of the Society for Neuroscience's,; 2009
Institución organizadora:
Society for Neuroscience
Migration of Bone Marrow mononuclear Cells and Remyelination of the crushed sciatic nerve. Vanina Usach, Belén Goitia and Patricia Setton-Avruj Department of Biological Chemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, IQUFIB, UBA-CONICET, IIMHNO-UBA, Buenos Aires, Argentina.             We have previously described in a model of ligated sciatic nerve and in a model of crushed sciatic nerve the decrease in P0 and MBP both in myelin isolated from the distal area of the injured nerve and in immunohistochemistry (IHC) studies.  In the ligated model we have also demonstrated the migration, either spontaneous or after intraortical injection, of fresh bone marrow mononuclear cells (BMMC) CD34+ to the distal stump of the nerve. In the crushed sciatic nerve we have shown the presence of injected BMMC 5 days post injury. According to our previous results the aim of the present work was to study the remyelination of the crushed sciatic nerve and to evaluate whether BMMC/ mesenchymal stem cells (MSC) migrated to the injured nerve in order to participate in the degeneration process and/ or in the regeneration process. For this purpose we studied the colocalization of BMMC/MSC with Schwann cells (SC)’ markers. Adult female Wistar rats were submitted to the crush of the right sciatic nerve and were sacrificed at different survival times. The nerve was dissected into proximal and distal areas; the left sciatic nerve, or contralateral nerve, was taken as a control. BMMC were isolated from the bone marrow extruded from tibia and femur bones from male rats. A group was immediately processed and the other was seeded. After 24-48hs the non-adherent cells were separated and the adherent cells were grown to confluence. Freshly isolated or cultured BMMC were dyed with a fluorescent probe and injected intravenously immediately after crushing the sciatic nerve in order to evaluate the migration of these cells to the injured area. IHC analyses of the crushed sciatic nerve were done to evaluate the demyelination-remyelination of the nerve as well as the phenotype of BMMCs once they reached the nerve. The results obtained by myelin isolation and by IHC demonstrated that the crushed sciatic nerve started the remyelination process 28 days after the injury, reaching normal levels of proteins by 60 days post injury. In the same model, we also demonstrated the spontaneous migration of CD34+ cells  to the ipsilateral nerve at 3 days post injury,  as well as the migration of labelled BMMC after transplantation of the cells intraarterially in the medium sacra artery. We also demonstrate the colocalization of BMMCs with S100, a universal SC marker, in the proximal and distal stump of the crushed sciatic nerve as well as in the crush area. More experiments are necessary to demonstrate whether the transplantation of SC transdifferentiated “in vitro” from MSC promotes better results than the transplantation of BMMC in order to choose the best cell population for future transplation therapies.  [_1]No en el abstract