Electronic Poster | Session 2
051 – Immunomodulatory action of bone marrow cell transplant in sciatic nerve injury
Gonzalo Piñero (1) – Marianela Vence (2) – Paula Soto (1) – Vanina Usach (1) – Patricia Setton-Avruj (1)
CONICET, Universidad de Buenos Aires, CABA, Argentina (1) – CONICET, IQUIFIB, CABA, Argentina (2)
Bone marrow cells include different cell types containing a minority multipotent fraction. For this reason, they 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, we have shown systemically transplanted bone marrow cells to spontaneously migrate to and remain in the injured nerve for as long as 60 days. A small number of these cells upregulated markers unexpressed before transplant, leading to cell phenotypic changes and transdifferentiation to Schwann cells, while a significantly larger proportion left the tissue once the inflammatory phase had finished. They also enhanced axonal regeneration and remyelination, promoted functional recovery and prevented lesion-induced hyperalgesia.
The aim of the present work is to evaluate whether transplanted bone marrow cells exert their well-established beneficial effect on sciatic nerve regeneration through immunomodulation. Adult C57BL/6 mice received intravenous transplantation of either bone marrow cells or vehicle after 8-second sciatic nerve crush. Along recovery, functional aspects were evaluated through hot plate and walking track tests. Animals were then sacrificed for immunohistochemistry, ELISA, qPCR and flow cytometry studies. The mouse model resembles results obtained in rats in terms of cell migration, histological and functional recovery. In order to study the immunomodulatory effects of cell therapy, we assessed the profile of the main cytokines involved and the phenotype of macrophages in the lesion area. So far, qPCR and flow cytometry assays have shown that cell transplant reduces the expression of pro-inflammatory markers and anticipates the expression of anti-inflammatory ones. Nevertheless, further studies are required to fully corroborate immunomodulation effects.