Immunogenicity of autologous and allogeneic human primary cholangiocyte organoids

Primary human cells cultured in 3D organoid format have great promise as
potential regenerative cellular therapies, but their immunogenicity has
not yet been fully characterized. In this study, we use in vitro
co-cultures and in vivo humanized mouse experimental models to examine the
human immune response to autologous and allogeneic primary cholangiocyte
organoids (PCOs). Our data demonstrate that PCOs upregulate the expression
of HLA-I and HLA-II in inflammatory conditions. The immune response to
allogeneic PCOs is driven by both HLA-I and HLA-II and is substantially
ameliorated by donor-recipient HLA matching. Autologous PCOs induce a
low-level immune infiltration into the graft site, while allogeneic cells
display evolving stages of immune rejection in vivo. Our findings have
important implications for the design and clinical translation of
autologous and allogeneic organoid cellular therapies.