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

SIERRA, ROMINA; GÓMEZ BUSTILLO, SOFÍA; FIORE, ESTEBAN J.; MAZZONE, GRACIELA L.; MONTANER ALEJANDRO D.; AQUINO, JORGE B.

Mar del Plata

Congreso; Reunión anual de Sociedades de Biociencia 2019 (SAB); 2019

Sociedad Argentina de Biología

Cirrhosis, the last stage of liver fibrosis,results from repeated cycles of liver damage and scar formationand is the first cause of liver transplant. Little is known regardingthe 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 BMGLAST+ cells to liver fibrogenesis and regeneration. Wnt1Cre2and GLASTCreERT(2);Rosa26Tomato mice were used. Two models of liver cirrhosis were generated: 1) repeatedapplications of thioacetamide and 2) bile duct ligation. Inaddition, a model of partial hepatectomy was applied. Thephenotype of BM, peripheral blood and liver traced-cells wasanalyzed by flow cytometry and immunostainings. Data from invivo studies suggest an activation of liver glia during fibrogenesisas well as increased numbers of traced endothelial cells. In bothtransgenic mice, some hepatocytes were traced and theyincrease in numbers in the fibrotic liver. Stromal cells within theBM were also traced in both mouse lines. BM cells were mobilizedduring fibrogenesis and Wnt1-traced cells formed pure stromalcolonies when attached to plastic. Application of IMT504 was ableto restore Wnt1-traced CFUs in the context of liver fibrogenesis.The incidence of CD44+ HNF4α+ GLAST-traced hepatocytesincreased in numbers during liver regeneration. Bone marrowGLAST- and/or Wnt1-traced cells likely contribute with liverregeneration in models of liver fibrogenesis and partialhepatectomy.