Generation of hypoimmunogenic cardiomyocytes from human induced pluripotent stem cells with TAPBP knockout

Abstract

Immunological rejection is a challenge for the transplantation of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs). TAP-binding protein knockout (TAPBP-KO) hiPSC-derived CMs (hiPSC-CMs) were used to reduce human leukocyte antigen class I expression and their hypoimmunogenic potential was determined. TAPBP-KO hiPSC-CMs exhibited CM differentiation efficiency and functional properties comparable to those of controls. The immunological responses against cytotoxic T lymphocytes (CTLs) or natural killer cells (NK cells) were measured using the production of inflammatory cytokines, the expression of degranulation markers, and cell viability upon co-cultivation with hiPSC-CMs. The CTL-mediated cytotoxicity was lower in TAPBP-KO hiPSC-CMs than in controls. TAPBP-KO hiPSC-CMs did not induce cytotoxicity from NK cells. This approach can preclude immunological rejection from CTLs without initiating the innate immune response from NK cells, thereby expanding the access to cell therapy for patients with heart failure.