TY - JOUR
T1 - Metabolic changes of human induced pluripotent stem cell-derived cardiomyocytes and teratomas after transplantation
AU - Soma, Yusuke
AU - Tohyama, Shugo
AU - Kubo, Akiko
AU - Yamasaki, Tomoteru
AU - Kabasawa, Noriko
AU - Haga, Kotaro
AU - Tani, Hidenori
AU - Morita-Umei, Yuika
AU - Umei, Tomohiko C.
AU - Sekine, Otoya
AU - Nakamura, Masashi
AU - Moriwaki, Taijun
AU - Tanosaki, Sho
AU - Someya, Shota
AU - Kawai, Yujiro
AU - Ohno, Masatoshi
AU - Kishino, Yoshikazu
AU - Kanazawa, Hideaki
AU - Fujita, Jun
AU - Zhang, Ming Rong
AU - Suematsu, Makoto
AU - Fukuda, Keiichi
AU - Ieda, Masaki
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/11/15
Y1 - 2024/11/15
N2 - Cardiac regenerative therapy using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has been applied in clinical settings. Herein, we aimed to investigate the in vivo metabolic profiles of hiPSC-CM grafts. RNA sequencing and imaging mass spectrometry were performed in the present study, which revealed that hiPSC-CM grafts matured metabolically over time after transplantation. Glycolysis, which was active in the hiPSC-CM grafts immediately after transplantation, shifted to fatty acid oxidation. Additionally, we examined the metabolic profile of teratomas that may form when non-CMs, including undifferentiated human induced pluripotent stem cells (hiPSCs), remain in transplanted cells. The upregulated gene expression of amino acid transporters and the high accumulation of amino acids, such as methionine and aromatic amino acids, were observed in the teratomas. We show that subcutaneous teratomas derived from undifferentiated hiPSCs can be detected in vivo using positron emission tomography with [18F]fluorophenylalanine ([18F]fPhe). These results provided insights into the clinical application of cardiac regenerative therapy.
AB - Cardiac regenerative therapy using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has been applied in clinical settings. Herein, we aimed to investigate the in vivo metabolic profiles of hiPSC-CM grafts. RNA sequencing and imaging mass spectrometry were performed in the present study, which revealed that hiPSC-CM grafts matured metabolically over time after transplantation. Glycolysis, which was active in the hiPSC-CM grafts immediately after transplantation, shifted to fatty acid oxidation. Additionally, we examined the metabolic profile of teratomas that may form when non-CMs, including undifferentiated human induced pluripotent stem cells (hiPSCs), remain in transplanted cells. The upregulated gene expression of amino acid transporters and the high accumulation of amino acids, such as methionine and aromatic amino acids, were observed in the teratomas. We show that subcutaneous teratomas derived from undifferentiated hiPSCs can be detected in vivo using positron emission tomography with [18F]fluorophenylalanine ([18F]fPhe). These results provided insights into the clinical application of cardiac regenerative therapy.
KW - cardiovascular medicine
KW - cell biology
UR - https://www.scopus.com/pages/publications/85208273763
UR - https://www.scopus.com/pages/publications/85208273763#tab=citedBy
U2 - 10.1016/j.isci.2024.111234
DO - 10.1016/j.isci.2024.111234
M3 - Article
AN - SCOPUS:85208273763
SN - 2589-0042
VL - 27
JO - iScience
JF - iScience
IS - 11
M1 - 111234
ER -