The role of neural crest-derived cells and/or bone marrow GLAST+ pericytes in liver fibrosis and regeneration

AQUINO JB

Chiclayo

Jornada; VI Jornada Internacional de Genética ?66 years of 46 Human Chromosomes? Últimos Avances en Genética y Biología Molecular; 2022

The International Circle of Genetic Studies

Liver fibrosis results from cycles of liver damage and scar formation. We have aimed at analyzing neural crest cells and/or bone marrow stromal cells (BMSCs) contribution to the liver. With this aims, two liver fibrosis and one hepatectomy model were applied on two double-transgenic mouse strains, Wnt1-Cre-Tom and GLAST-CreERT2-Tom. During liver fibrogenesis, increased numbers of glia cells with more complex processes were found in this tissue. In the fibrotic liver, a significantly higher incidence of endothelial-like cells (ELCs) and hepatocyte-like cells (HLCs) expressing the reporter gene Tomato were observed. Consistently, during early liver fibrogenesis Wnt1-traced BMSCs, with progenitor (CFU-F) properties, get likely mobilized to peripheral blood. Furthermore, in a 70% hepatectomy model, GLAST+ Wnt1-traced BMSCs were found to be mobilized from the bone marrow and contribute with ELCs and HLCs in the liver. IMT504 was found to further increase the recruitment of GLAST+ Wnt1+ BMSCs into the injured liver and the incidence of ELCs and HLCs. A similar mechanism might be involved in myocardial repair after infarction. Our data suggest a gliosis process during liver fibrogenesis. While neural crest cells probably do not contribute with other liver cell types than glia, GLAST+ Wnt1-traced BMSCs are a population of progenitors which are likely a source of ELCs and HLCs after liver injury.