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.

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BibTeX RIS

BibTeX

@article{yamamoto2026generation,
  title = {{Generation of hypoimmunogenic cardiomyocytes from human induced pluripotent stem cells with TAPBP knockout}},
  author = {Yuki Yamamoto and Rei Ohno and Kayoko Shoda and Toshihiro Suzuki and Kuniko Momoi and Shohei Fujii and Yuka Kenmochi and Toshiaki Yoshikawa and Manami Shimomura and Nobuo Tsukamoto and Kazunobu Ohnuki and Hidenori Tani and Yusuke Soma and Keiichi Fukuda and Tetsuya Nakatsura and Shugo Tohyama},
  journal = {iScience},
  year = {2026},
  month = oct,
  doi = {10.1016/j.isci.2026.117933},
  url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03316-X},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - Generation of hypoimmunogenic cardiomyocytes from human induced pluripotent stem cells with TAPBP knockout
AU  - Yuki Yamamoto
AU  - Rei Ohno
AU  - Kayoko Shoda
AU  - Toshihiro Suzuki
AU  - Kuniko Momoi
AU  - Shohei Fujii
AU  - Yuka Kenmochi
AU  - Toshiaki Yoshikawa
AU  - Manami Shimomura
AU  - Nobuo Tsukamoto
AU  - Kazunobu Ohnuki
AU  - Hidenori Tani
AU  - Yusuke Soma
AU  - Keiichi Fukuda
AU  - Tetsuya Nakatsura
AU  - Shugo Tohyama
PY  - 2026
DA  - 2026/10/17
JO  - iScience
DO  - 10.1016/j.isci.2026.117933
UR  - https://www.cell.com/iscience/fulltext/S2589-0042(26)03316-X
AB  - 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.
SN  - 2589-0042
ER  -

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