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

AQUINO, JORGE B.; SIERRA, ROMINA

Mar del Plata

Congreso; SAIC; 2019

SAIC

ntroduction: Cirrhosis, the last stage of liver fibrosis, results from repeated cycles of liver damageand scar formation and is the first cause of liver transplant. Little is known regarding thecontribution 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. M&M: Wnt1 Cre2 and GLAST CreERT(2) ;Rosa26 Tomato mice wereused. Two models of liver cirrhosis were generated: 1) repeated applications of thioacetamide and2) bile duct ligation. In addition, a model of partial hepatectomy was applied. The phenotype ofBM, peripheral blood and liver traced-cells was analyzed by flow cytometry and immunostainings.Results: Data from in vivo studies suggest an activation of liver glia during fibrogenesis as well asincreased numbers of traced endothelial cells. In both transgenic mice, some hepatocytes weretraced and they increase in numbers in the fibrotic liver. Stromal cells within the BM were alsotraced in both mouse lines. BM cells were mobilized during fibrogenesis and Wnt1-traced cellsformed pure stromal colonies when attached to plastic. Application of IMT504 was able to restoreWnt1-traced CFUs in the context of liver fibrogenesis. The incidence of CD44+ HNF4α+ GLAST-traced hepatocytes increased in numbers during liver regeneration. Conclusions: Bone marrowGLAST- and/or Wnt1-traced cells likely contribute with liver regeneration in models of liver fibrogenesis and partial hepatectomy.