Contribution of neural crest derived-cells and bone marrow GLAST+ cells to the liver

SIERRA R; GÓMEZ S; FIORE E; MAZZONE G; MONTANER A; AQUINO JB

CABA

Congreso; Annual Meeting SAIC, SAFE, SAB, SAP; 2019

SAIC, SAFE, SAB, SAP

Abstract/Resumen: Cirrhosis, the last stage of liver fibrosis, results from repeated cycles of liver damage and scar formation and is the first cause of liver transplant. Little is known regarding the contribution of neural crest-derived cells and bone marrow (BM) to the liver in health and disease. Objective: The aim of this work was to analyze the role of neural crest-derived and/or BM-GLAST+ cells to liver fibrogenesis and regeneration. Wnt1Cre2 and GLASTCreERT(2);Rosa26Tomato mice were used. Two models of liver cirrhosis were generated: 1) repeated applications of thioacetamide and 2) bile duct ligation. In addition, a model of partial hepatectomy was applied. The phenotype of BM, peripheral blood and liver traced-cells was analyzed by flow cytometry and immunostainings. Data from in vivo studies suggest an activation of liver glia during fibrogenesis as well as increased numbers of traced endothelial cells. In both transgenic mice, some hepatocytes were traced and they increase in numbers in the fibrotic liver. Stromal cells within the BM were also traced in both mouse lines. BM cells were mobilized during fibrogenesis and Wnt1-traced cells formed pure stromal colonies when attached to plastic. Application of IMT504 was able to restore Wnt1-traced CFUs in the context of liver fibrogenesis. The incidence of CD44+ HNF4α+ GLAST-traced hepatocytes increased in numbers during liver regeneration. Bone marrow GLAST- and/or Wnt1-traced cells likely contribute with liver regeneration in models of liver fibrogenesis and partial hepatectomy.