Engineering Human Pluripotent Stem Cell Lines to Evade Xenogeneic Transplantation Barriers.

ABSTRACT: Allogeneic human pluripotent stem cell (hPSC)-derived cells and tissues for therapeutic transplantation must necessarily overcome immunological rejection by the recipient. To define these barriers and to create cells capable of evading rejection for preclinical testing in immunocompetent mouse models, we genetically ablated β2m, Tap1, Ciita, Cd74, Mica, and Micb to limit expression of HLA-I, HLA-II, and natural killer cell activating ligands in hPSCs. Though these and even unedited hPSCs readily formed teratomas in cord blood-humanized immunodeficient mice, grafts were rapidly rejected by immunocompetent wild-type mice. Transplantation of these cells that also expressed covalent single chain trimers of Qa1 and H2-K^b to inhibit natural ki

SUBMITTER: Pizzato HA 

PROVIDER: S-EPMC10326974 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature