Title:Immunogenicity and Immunomodulatory Properties of Hepatocyte-like Cells Derived from Human Amniotic Epithelial Cells
VOLUME: 8 ISSUE: 1
Author(s):Jing Yang Tee, Vijesh Vaghjiani, Yu Han Liu, Padma Murthi, James Chan and Ursula Manuelpillai
Affiliation:Monash Institute of Medical Research, 27-31 Wright Street, Clayton, Victoria 3168, Australia
Keywords:Amniotic epithelial cells, anti-inflammatory cytokines, fetal membranes, hepatocyte-like cells, immunogenicity,
immunomodulation, PGE2, IL-6, lymphocyte reactions, Hepatocyte transplantation.
Abstract:Hepatocyte transplantation is being trialled as an alternative to whole organ transplant for patients with acute
liver failure and liver specific metabolic diseases. Due to the scarcity of human hepatocytes, hepatocyte-like cells (HLC)
generated from stem cells may become a viable alternative to hepatocyte transplantation. Human amniotic epithelial cells
(hAEC) from the placenta have stem cell-like properties and can be differentiated into HLC. Naïve hAEC have low immunogenicity
and exert immunomodulatory effects that may facilitate allogeneic transplantation. However, whether the
immunogenicity and immunomodulatory properties alter with differentiation into HLC are unknown. We further characterized
HLC generated from hAEC, examined changes in human leucocyte antigens (HLA) and co-stimulatory molecules
and effects exerted by the HLC on human peripheral blood mononuclear cells (PBMC). HLC derived from hAEC expressed
proteins found in hepatocytes, had CYP3A4 drug metabolizing enzyme activity and secreted urea. IFN-γ treatment
increased HLA Class IA, Class II and co-stimulatory molecule CD40 expression in the HLC. IFN-γ treated HLC
stimulated proliferation of PBMC in one-way mixed lymphocyte reactions and were more immunogenic than undifferentiated
hAEC. However, the HLC showed immunomodulatory properties and inhibited mitogen induced PBMC proliferation
in vitro. PBMC proliferation may have been inhibited by IL-6, TGF-β1, PGE2 and HLA-G secreted by the HLC. The
retention of immunomodulatory properties may enable HLC grafts to survive for longer periods despite the immunogenicity
of the HLC.
