Engineering human stem cell-derived islets to evade immune rejection and promote localized immune tolerance.

ABSTRACT: Immunological protection of transplanted stem cell-derived islet (SC-islet) cells is yet to be achieved without chronic immunosuppression or encapsulation. Existing genetic engineering approaches to produce immune-evasive SC-islet cells have so far shown variable results. Here, we show that targeting human leukocyte antigens (HLAs) and PD-L1 alone does not sufficiently protect SC-islet cells from xenograft (xeno)- or allograft (allo)-rejection. As an addition to these approaches, we genetically engineer SC-islet cells to secrete the cytokines interleukin-10 (IL-10), transforming growth factor β (TGF-β), and modified IL-2 such that they promote a tolerogenic local microenvironment by recruiting regulatory T cells (T_regs) to the islet grafts. Cytokine-secreting human SC-β cells re

SUBMITTER: Gerace D 

PROVIDER: S-EPMC9873825 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature