Cross talk between Bone Marrow Mononuclear Cells and immune system cells in Peripheral Nervous System remyelination

GONZALO PIÑERO; PAULA A, SOTO; VANINA USACH; DANIELA GENARO; CLARA P. SETTON

Mar del Plata

Congreso; XXIX Congreso Anual Sociedad Argentina de Neurociencias; 2015

Sociedad Argentina de Neurociencias

Wallerian degeneration (WD) is a pathophysiological process characterized by demyelination and axonal degeneration. Immediately after injury, the interruption of Schwann cell (SC) and axon dialogue generates SC dedifferentiation. Along with fibroblasts, these SC secrete cytokines such as IL-1β, IL-6, TNFα, GM-CSF, CCL2 and CCL3, which promote immune cell infiltration as from 24h 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 and contributing to axonal regrowth through IL-10, TGFβ and trophic factor secretion.Bone marrow mononuclear cell (BMMC) transplant has recently become relevant in multiple pathologies, including peripheral nervous system (PNS) lesions. To test the hypothesis that BMMC effects involve immunomodulatory actions, the present work evaluated BMMC remyelination ability and cytokine mRNA levels in adult rats undergoing sciatic nerve crush. Epifluorescent, confocal, optical and electronic microscopy and Western blot analyses showed axonal recovery and remyelination promoted by cell transplant. As regards cytokine secretion, qPCR studies performed 24h post injury proved BMMC transplant to promote a decrease in IL-1β levels compared to non-transplanted rats. Macrophage polarization assays are now under way in order to further confirm a cross talk between BMMC and immune system cells in PNS remyelination.