Contribution of Neural Crest derived cells and GLAST+ pericytes in liver regeneration during Fibrogenesis and Cirrhosis

SIERRA R; BLANCO MV; BORTH C; FIORE EJ; AQUINO JB

San Francisco

Congreso; Liver Meeting ® 2018; 2018

American Association for the Study of Liver Diseases (AASLD)

Background: Cirrhosis is the last state of liver fibrosis, results from repeated cycles of liver damage and scar formation and is number one cause of liver transplant. Little is known regarding the contribution of neural crest‐derived cells (NCDCs) to the liver in health and disease. Although this tissue seems to be largely devoid of Peripheral Nervous System (PNS) cells, previous findings, based on in vivo mouse genetic lineage‐tracing studies likely suggest that some hepatocyte‐like cells (HLCs) might be of this origin. Objective: The aim of this work was to analyze the role of NCDCs and GLAST+ pericytes to the liver regeneration during fibrogenesis Methods: Wnt1Cre2;R26RTom and GLASTCreERT(2) mice were mated with Rosa26‐loxP‐Tomato. Two models of liver cirrhosis were generated: 1) chronic applications of thioacetamide (200mg/kg per dose; i.p.; 3 doses per week; survival: 1, 4 and 8 weeks), and 2) bile duct ligation (survival: 2 weeks). The co‐expression of the reporter gene with hepatocyte cell markers was analyzed by flow cytometry and immunofluorescence. Contribution of NCDCs and GLAST+ pericytes from bone marrow to liver was analyzed by flow cytometry as wells as migration through peripheral blood. For analysis of bone marrow NCDCs, the colony forming units‐fibroblasts (CFU‐F) assay was performed in both cirrhotic and healthy animals Results: Data from in vivo studies with Wnt1‐Cre2:Rosa26‐Tomato and GLAST‐CreERT (2) Rosa26‐Tomato mice demonstrated a contribution of NCDCs with HLCs in the adult. Animals with no damage showed a small number of Neural crest derived HCLs in the liver. Fibrogenesis was found to induce a significant increase in numbers of this HLCs (p