Hypoimmunogenic hPSC-derived cardiac organoids for immune evasion and heart repair.

ABSTRACT: Human pluripotent stem cell (hPSC)-derived cardiac therapies hold great promise for heart regeneration but face major translational barriers due to allogeneic immune rejection. Here, we engineered hypoimmunogenic hPSCs using a two-step CRISPR-Cas9 strategy: (1) B2M knockout, eliminating HLA class I surface expression, and (2) knock-in of HLA-E or HLA-G trimer constructs in the AAVS1 safe harbor locus to confer robust immune evasion. Hypoimmunogenic hPSCs maintained pluripotency, efficiently differentiated into cardiac cell types that resisted both T and NK cell-mediated cytotoxicity in vitro, and self-assembled into engineered cardiac organoids. Comprehensive analyses of the hypoimmunogenic cells and organoids revealed preservation of transcriptomic, structural, and functional prope

SUBMITTER: Silver SE 

PROVIDER: S-EPMC12027337 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature