Cross talk between BMMC and immune system cells in PNS remyelination

PIÑERO, GONZALO; SOTO, PAULA; USACH, VANINA; GENARO DANIELA; SETTON - AVRUJ, PATRICIA

Mar del Plata, Argentina

Congreso; XXX Congreso Anual Sociedad Argentina de Neurociencias (SA; 2015

Wallerian degeneration (WD) is a pathophysiological process characterized by demyelination and axonal degeneration, reflected in alterations in myelin and axonal protein levels and organization. Immediately after injury, the interruption of Schwann cell (SC) and axon communication generates SC dedifferentiation. Along with fibroblasts, these SC secrete cytokines such as IL1β, IL-6, TNFα, GM-CSF, CCL2 and CCL3, which promote immune cell infiltration as from 24 hours post injury.Among other cell types, hematogenous macrophages and the few resident ones take over as the dominant leukocyte population playing a critical role in ensuring complete WD through debris phagocytosis as well as contribute to axonal regrowth through secretion of IL-10, TGFβ and tropic factors.In the last few years, bone marrow mononuclear cell (BMMC) transplant has become relevant in multiple pathologies, including peripheral nervous system lesions, through immunomodulatory actions. To confirm this hypothesis, the present work evaluate BMMC remyelination ability in adult rats undergoing 8-second sciatic nerve crush as well as cytokine mRNA levels in animals receiving or not BMMC transplantation.Epifluorescence, confocal, optical and electronic microscopy and Western blot analyses demonstrate axonal recovery and remyelination promoted by cell transplant.As regard cytokines secretion qPCR studies performed at 24h and 4 days post injury, demonstrate that BMMC transplant promote a decrease in IL-1β levels compared to non-treated rats. Macrophage polarization analyses are currently ongoing in order to establish the existence of a cross talk between BMMC and immune system cells in PNS remyelination.