Contribution of neural crest and GLAST + Wnt1 + bone marrow pericytes with liver fibrogenesis and/or regeneration

SIERRA, ROMINA; GÓMEZ BUSTILLO, SOFÍA; KAMENEVA, POLINA; FIORE, ESTEBAN J.; MAZZONE, GRACIELA L.; BORDA, MAXIMILIANO; BLANCO, MARÍA V.; USUARDI, CHIARA; FURLAN, ALESSANDRO; ERNFORS, PATRIK; ALANIZ, LAURA; MONTANER, ALEJANDRO D.; ADAMEYKO, IGOR; AQUINO, JORGE B.

LIVER INTERNATIONAL

WILEY-BLACKWELL PUBLISHING, INC

Año: 2020 vol. 40 p. 977 - 987

1478-3223

Background and aims: Liver fibrosis results from cycles of liver damage and scar formation. We herein aimed at analysing neural crest cells and/or bone marrow stromal cells contribution to the liver.Methods: Two liver fibrosis and one hepatectomy model were applied on double-transgenic loxP-Cre mouse lines.Results: Increased numbers of glia with more complex processes were found in fibrotic livers. During embryonic development, only few cells were traced in the liver and bone marrow, in a minor fraction of mice of different neural crest reporter strains analysed: therefore, a neural crest origin of such cells is doubtful. In the fibrotic liver, a significantly higher incidence of endothelial cells and hepatocyte-like cells expressing the reporter gene Tomato were found in Wnt1-Cre-Tom and GLAST-CreERT2-Tom mice. Consistently, during early fibrogenesis stromal Wnt1-traced cells, with progenitor (CFU-F) properties, get likely mobilized to peripheral blood. Circulating adult Wnt1-traced cells are stromal cells and lack from the expression of other bone marrow and endothelial progenitor cells markers. Furthermore, in a 70% hepatectomy model GLAST+ Wnt1-traced pericytes were found to be mobilized from the bone marrow and the incidence of GLAST-traced hepatocyte-like cells was increased. Finally, GLAST-traced hepatocyte like-cells were found to maintain the expression of stromal markers.Conclusions: 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 bone marrow pericytes are likely a source of endothelial and hepatocyte-like cells after liver injury and do not contribute to scarring.