IMT504 enhances the contribution of GLAST+ Wnt1+ bone marrow stromal progenitors with hepatocyte-like cells and endothelial-like cells in the fibrotic liver

BORDA M; CANTERO MJ; FIORE EJ; BAYO FINA JM; SIERRA R; GÓMEZ-BUSTILLO S; ABALO A; GIARDELLI G; MONTANER A; AQUINO JB

Mar del Plata

Congreso; Annual Meeting SAIC, SAI, FAIC, SAFIS; 2022

SAIC, SAI, FAIC, SAFIS

Objectives: To evaluate the effect of IMT504 on fibrogenesis and the contribution of bone marrow stromal cells (BMSCs) subpopulations with hepatic tissue we used GLASTCreERT2; Rosa26Tom mice. Materials and methods: Liver fibrosis was established by thioacetamide applications during 8 weeks, and animals were s.c. treated with 1 or 3 doses of IMT504. Liver fibrosis degree was determined by red Sirius staining and the phenotype of Tom+ analyzed by immunofluorescence. For in vitro assays, Tom+ and Tom- BMSC subfractions were separately incubated with IMT504 for 2 hours and their proliferative and motility capacities were analyzed by flow cytometry and Boyden chamber. Results: IMT504 treatment was found to dose-dependently ameliorate liver fibrosis and to enhance hepatocyte proliferation. Application of 1 dose of IMT504 was shown to increase the incidence of hepatocyte-like Tom+ cells and endothelial-like Tom+ cells, an effect that was further significant in animals which received 3 doses of this oligonucleotide. Consistently, IMT504 induced the proliferation and motility of Tom+ BMSCs, with minimal effects on the Tom- fraction. Conclusions: IMT504 was found to reduce collagen deposition in a mouse liver fibrosis model and to enhance the contribution of Tom+ BMSCs with parenchymal and endothelial liver cells, likely through the induction of proliferation and migration of GLAST+ Wnt1+ bone marrow progenitors.