Human amniotic epithelial stem cells: Involvement of WNT/ΒETA-catenin signalling during their hepatic differentiation

ANTONIO PÉREZ-PÉREZ; ROBERTO CASALE; JULIETA LORENA MAYMÓ; RODRIGO RIEDEL; ORNELLA PAROLINI; CECILIA LAURA VARONE; MARIANA JAIME; VICTOR SÁNCHEZ MARGALET

Bogotá

Congreso; IX SLIMP-Latin American Society for Materno Fetal Interaction and Placenta.; 2022

SLIMP-Latin American Society for Materno Fetal Interaction and Placenta.

Objectives: The amniotic membrane from the human placenta at term is an important stem cell source, including human amniotic epithelial stem cells (hAECs). They express embryonic stem cells markers, and they are pluripotent. These characteristics position hAECs as ideal candidates for regenerative medicine. Hepatic failure is one of the major causes of morbidity and mortality worldwide. The available treatments have several obstacles. Recently, hAECshave been spotlighted as an alternative source of hepatocytes because of their potential for hepatogenic differentiation. The Wnt/beta-catenin pathway is an evolutionarily conserved signaling cascade that is important for stem cell renewal, cell proliferation, and cell differentiation, including hepatogenesis. This work aimed to assess the Wnt/beta-catenin pathway participation during hepatic differentiation of hAECs.Methods: Previously, we have demonstrated that hAECs efficiently differentiate to hepatic-like cells, by applying a specific hepatic differentiation (HD) protocol.Results: We have found that HD medium significantly induced an increment in Wnt-1, beta-catenin, and E-cadherin expression in hAECs, measured by qRT-PCR and Western blot. We have also observed a significant increment in E-cadherin nuclear localization during hAECs HD, evaluated by immunofluorescence. Moreover, HD decreased GSK3-B expression. Treatment of hAECs with XAV939 (a beta-catenin pathway inhibitor) caused the inhibition of HD, as albumin and CYP7A1 expression were reduced. Additionally, beta-catenin pathway inhibition during HD, diminished the expression of miRNAs involved in liver development (mir-122, mir-221, and mir-194).Conclusion: These results suggest that the Wnt/beta-catenin pathway activation may be responsible for successful hepatic differentiation of hAECs. Understanding the molecular mechanisms regulating hepatocyte differentiation will significantly facilitate the development of stem cell-based therapy to treat liver diseases.