HUMAN BILIARY TREE STEM/PROGENITOR CELLS (hbTSCS) FROM PERIBILIARY GLANDS (PBGS) OF ADULT LIVER DISPLAY IMMUNOMODULATORY PROPERTIES THROUGH Fas/Fas LIGAND INDUCED T-CELL LYMPHOCYTE APOPTOSIS

Background and Aims: hBTSCs have the potential for regenerative
medicine in liver and pancreas diseases. T-cell control was recently
demonstrated for mesenchymal stem cells. The aims of this study
were to evaluate Fas-L expression within the stem cell niches of
adult biliary tree (PBGs), and to study the interaction between
hBTSCs and human lymphocytes.
Methods: HLA antigens, Fas and Fas-L expression were evaluated by
immunofluorescence and western blotting (WB) in cells of human
biliary tree in comparison with fibroblast cells, dental pulp stem
cells and bone marrow mesenchymal stem cells. The influence of
hBTSCs on lymphocytes’ activation and apoptosis were assessed by
co-culturing experiments.
Results: Adult hBTSCs expressed both class I and class
II HLA antigens, whereas fetal hBTSCs only class I HLA
antigens. 10 to 30% of the hBTSCs in PBGs were positive
for Fas-L. Fas-L+ cells were mostly located at the bottom
of PBGs and co-expressed EpCAM (Epithelial-Cell-AdhesionMolecule)
and proliferation marker (PCNA:Proliferating-CellNuclear-Antigen).
Mature cells at the bile duct surface epithelium
(mature cholangiocytes) were almost all negative for Fas-L. In
culture experiments confocal microscopy demonstrated that Fas-L
expression was restricted to EpCAM+/LGR5+ (a marker associated
with endodermal stem cells) hBTSCs. WB confirmed that hBTSCs
constitutively expressed high level of Fas-L which increased after
co-culture with T-cells. FACS analysis reveled that activated CD4+
and CD8+ T-cells co-cultured with hBTSCs underwent to a massiveinduction of apoptosis. Fas receptor appeared over-expressed in
T-cells co-cultured with hBTSCs respect to resting T-cells.
Conclusions: Our data demonstrated that hBTSCs can induce
“premature” apoptosis in T-cells trough the activation of Fas/Fas-L
pathway