Bone marrow pluripotent cells: their starring role in nerve regeneration and recovery.

USACH VANINA; CASALI CI; LAVALLE L; GONZALO PIÑERO; WEBER K; PARRA LEANDRO; FERNÁNDEZ TOMÉ MC; CLARA P. SETTON

Buenos Aires

Simposio; Official World Congress of Pain Satellite Meeting hosted byThe Pain and Pain Management in Non-Human Species Special Interest Group: From stem cells to meta-analysis ? a broad picture of modern approaches to preclinical pain research; 2014

International Association to Study Pain

Bone marrow pluripotent cells: their starring role in nerve regeneration and recovery. V. Usach, C. Casalis, L. Lavalle, G. Piñero, K. Weber, A. Brusco, M. Fernández Tomé, P. Setton-Avruj Abstract As sciatic nerve demyelination is a process associated to neuropathic pain, experimental models which explore recovery strategies may prove essential to pain-ammeliorating therapies. In this perspective, we have previously described the clustering of major myelin proteins MBP and P0 and axonal protein PGP 9.5 during sciatic nerve demyelination, as well as the migration of both endogenous and transplanted CD34+ bone marrow mononuclear cells (BMMC) exclusively to the injured nerve. Once in the ipsilateral nerve, some BMMC remain CD34+ (pluripotent), while others colocalize with Schwann cell and nerve fiber markers. In this context, the aim of the present work was to evaluate the participation of BMMC in the demyelination-remyelination process and to determine whether lesion-associated inflammation is involved in cell recruitment. To such ends, adult Wistar rats were submitted to sciatic nerve crush and immediately intravenously transplanted with either BMMC or vehicle. The presence of BMMC in the injured nerve was then evaluated through confocal microscopy 24 hours, 3 and 5 days post injury. Electron microscopy was performed 3, 7 and 14 days post injury for nerve ultra-structural analysis and immunohistochemycal were conducted to evaluate myelin and nerve fiber protein organization. In order to analyse the involvement of inflammation in cell recruitment, the effect of indomethacin on cell migration, the expression of ciclooxygenase (Cox) and the synthesis of prostaglandins (PG) were evaluated. Results showed BMMC arrival at the edge of the nerve as from 24 hours post-transplant and integration to the nerve 2 days later. In terms of BMMC effect, results showed a marked decrease in MBP and P0 clusters, as well as nearly normal myelinated axons in the crush area. In turn, Cox-2 expression was induced, mostly in the ipsilateral nerve, 2 hours after nerve injury and continued at 24 hours. Treatment with indomethacin blocked BMMC migration but did not inhibit PG synthesis, as evidenced by an increase in PG J2. These data suggest that BMMC might stimulate remyelination through myelin debris removal or neuroimmunomodulatory actions, i.e. transdifferentiating to SC and/or releasing trophic factors. Further experiments will be necessary to elucidate other molecules and mechanisms involved in BMMC migration and their effect in the degeneration-regeneration process.