Contribución de la cresta neural y/o de células GLAST+ de la médula ósea con el hígado durante la fibrogénesis y la regeneración

AQUINO JB

Seminario; Ciclo de Seminarios del Instituto de Investigaciones en Medicina Traslacional CONICET-U. Austral; 2019

IIMT CONICET-Univ. Austral

Liver fibrosis results from cycles of liver damage and scar formation. Little is known regarding contribution of neural crest cells to the liver. We have herein used different double-transgenic lines and two models of liver fibrosis as well as one model of partial hepatectomy. Increased numbers of liver glia, with more ramified and extended processes, were found in fibrotic livers. Moreover, Schwann cell precursors (SCPs) were found to contribute with bone marrow stromal cells during embryonic stages, through peripheral blood circulation. In the fibrotic liver, a significantly higher incidence of Wnt1- and GLAST-traced endothelial cells and hepatocyte-like cells (HLCs) were observed when compared to control animals. Consistently, during early fibrogenesis Wnt1-traced cells get likely mobilized to peripheral blood. All mobilized Wnt1-traced cells co-expressed GLAST and CD44, a subpopulation showing CFU-F properties. A similar feature was observed in a 70% hepatectomy model. Application of the oligonucleotide IMT504 was able to restore numbers of CFU-F in the bone marrow of thioacetamide-treated mice and to increase the incidence of traced HLCs in the fibrotic liver of GLASTCreERT2:Rosa26Tom mice, with possible involvement of Wnt1 signaling. Finally, GLAST-traced HLCs in the hepatectomy model were found to co-express CD44. Our results might suggest contribution of neural crest derived cells from the bone marrow to tissue regeneration/remodeling.