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Presenter: Bart, Roep, Leiden, Netherlands
Authors: Bart Roep
Human embryonic stem cells (hESC) have great potential to provide an unlimited alternative source of beta-cells to overcome the donor shortage in islet transplantation to treat advanced type 1 diabetes. Given hESC may have immune privileged properties, it is important to determine if these properties are preserved in hESC-derived cells. We investigated immunological properties of hESC-derived pancreatic progenitor cells, and further in vivo differentiated hESC-derived endocrine cells by assessing HLA and complement receptor expression and exposure to alloreactive antibodies and cytotoxic T-cells and autoimmune cytotoxic T-cells. hESC-derived pancreatic endoderm expresses relatively low levels of HLA endorsing protection from specific immune responses. HLA was upregulated when exposed to interferon gamma (IFNγ), making these endocrine progenitor cells vulnerable to cytotoxic T-cells and alloreactive antibodies. In vivo differentiated endocrine cells were protected from complement, but expressed more HLA and were targets for alloreactive antibody-dependent cellular cytotoxicity and alloreactive cytotoxic T-cells. After HLA compatibility was provided by transduction with HLA-A2, preproinsulin specific T-cells killed insulin producing cells. Thus, hESC-derived pancreatic progenitors are hypoimmunogenic, while in vivo differentiated endocrine cells represent mature targets to adaptive immune responses. Our data support the need for immune intervention in transplantation of hESC-derived pancreatic progenitors. Cell-impermeable macro-encapsulation may suffice.
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