Hepatic differentiation of human amniotic epithelial cells and in vivo therapeutic effect on animal model of cirrhosis

Abstract

hAECs were able to differentiate into functional hepatocyte-like cells both in vivo and in vitro. They showed therapeutic efficacy after transplantation in mice model of cirrhosis, offering an exciting source of cells for generation of functionally useful hepatocytes.

Concise Review: Fetal Membranes in Regenerative Medicine: New Tricks from an Old Dog?

“…This study showed that allogeneic and xenogeneic fetal membrane derived stem cells were similarly efficacious in reducing neutrophil infiltration and fibrosis associated with bleomycin instillation . These reports suggest that hAEC, hAMSC and hCMSC may be of use in clinical pulmonary fibrosis , particularly given their ability to reverse established lung fibrosis . This approach may also be applied toward chronic obstructive pulmonary disease.…”

“…This outcome was attributed to their polarization of macrophages from proinflammatory M1 to pro-regenerative M2 [84], as well as directly effects on hepatic stellate cells [85]. In the setting of thioacetamideinduced chronic liver failure, intrasplenically transplanted hAEC showed therapeutic efficacy while preserving HLA-G expression [86]. These differentiated hAEC showed evidence of bile canaliculi, albumin secretion, indo-cyanine green elimination, low-density lipoprotein uptake, and inducible CYP3A4 and CYP2C9 enzyme function [86].…”

“…In the setting of thioacetamideinduced chronic liver failure, intrasplenically transplanted hAEC showed therapeutic efficacy while preserving HLA-G expression [86]. These differentiated hAEC showed evidence of bile canaliculi, albumin secretion, indo-cyanine green elimination, low-density lipoprotein uptake, and inducible CYP3A4 and CYP2C9 enzyme function [86]. These anti-fibrotic and pro-regenerative properties in liver disease have recently culminated in a first-in-man Phase 1b clinical trial for compensated liver cirrhosis (ACTRN12616000437460).…”

Enhanced hepatic differentiation of human amniotic epithelial cells on polyethylene glycol-linked multiwalled carbon nanotube-coated hydrogels

“…It has been reported that isolated hAECs resemble hepatic progenitor cell behaviours, such as ALB secretion (Sakuragawa et al, ; Takashima, Ise, Zhao, Akaike, & Nikaido, ) and expression of a subset of hepatocyte‐related markers including CK18, AFP, and α1AT (Moritoki et al, ; Takashima et al, ). These properties make hAECs a promising cell source for liver engineering (Lin et al, ; Marongiu et al, ; Vaghjiani et al, ). Our claim of hAECs differentiation is qualified by a combination of stem cell and hepatic marker changes.…”

“…To induce hepatic differentiation of hAECs (80,000 cells/cm 2 ), defined medium was used at different stages during 18 days' incubation. The hepatic induction was performed with a four‐step protocol as described previously (Lin et al, ): (a) growth medium supplemented with B‐27 (Biotool, USA) and 100 ng/ml Activin A (PeproTech, USA) from Day 1 to Day 5; (b) growth medium supplemented with B‐27, 20 ng/ml bone morphogenetic protein‐4 (Gibco, USA) and 10 ng/ml fibroblast growth factor‐2 (BD Bioscience, USA) from Day 6 to Day 10; (c) growth medium supplemented with B‐27 and 20 ng/ml hepatocyte growth factor (PeproTech, USA) from Day 11 to Day 15; and (d) hepatocyte culture medium (Lonza, Switzerland) supplemented with 20 ng/ml oncostatin M (R&D Systems, USA) and 100 μ m sodium taurocholate (Sigma‐Aldrich, USA) from Day 16 to Day 18.…”