Metabolic changes of human induced pluripotent stem cell-derived cardiomyocytes and teratomas after transplantation
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 <i>in vivo</i> 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 <i>in vivo</i> using positron emission tomography with [<sup>18</sup>F]fluorophenylalanine ([<sup>18</sup>F]fPhe). These results provided insights into the clinical application of cardiac regenerative therapy.
Authors
- Tomoteru Yamasaki (ORCID: https://orcid.org/0000-0001-7773-3665)
- Masashi Nakamura (ORCID: https://orcid.org/0000-0001-5248-5896)
- Y Soma (ORCID: https://orcid.org/0000-0003-2150-5465)
- Jun Fujita (ORCID: https://orcid.org/0000-0002-4522-0301)
- Shota Someya (ORCID: https://orcid.org/0000-0003-1064-1373)
- Masaki Ieda (ORCID: https://orcid.org/0000-0003-4724-3299)
- Otoya Sekine
- Hideaki Kanazawa (ORCID: https://orcid.org/0000-0002-0934-3910)
- Makoto Suematsu (ORCID: https://orcid.org/0000-0002-7165-6336)
- Yoshikazu Kishino (ORCID: https://orcid.org/0000-0003-3291-2795)
- Taijun Moriwaki (ORCID: https://orcid.org/0000-0002-0432-3363)
- Kotaro Haga (ORCID: https://orcid.org/0000-0003-2697-2097)
- Noriko Kabasawa
- Tomohiko Umei (ORCID: https://orcid.org/0000-0003-0294-6732)
- Keiichi Fukuda (ORCID: https://orcid.org/0000-0003-1413-0482)
- Sho Tanosaki
- Shugo Tohyama (ORCID: https://orcid.org/0000-0002-5898-3543)
- Akiko Kubo (ORCID: https://orcid.org/0000-0002-6003-227X)
- Yuika Morita-Umei
- Yujiro Kawai
- Hidenori Tani (ORCID: https://orcid.org/0000-0002-5042-6187)
- Masatoshi Ohno
- Ming-Rong Zhang
Institutions
- American Heart Association (US)
- Fujita Health University (JP)
- Baylor College of Medicine (US)
- Keio University (JP)
- Central Institute for Experimental Animals (JP)
- Innovation Center of NanoMedicine (JP)
- National Institutes for Quantum Science and Technology (JP)
Publication Details
- Journal
- iScience
- Published
- 2024-10-23
- DOI
- https://doi.org/10.1016/j.isci.2024.111234
- Citations
- 3
- Primary Topic
- Pluripotent Stem Cells Research
- Type
- article
- Field-Weighted Citation Impact
- 0.70
Funders
- Japan Agency for Medical Research and Development
- Kanagawa Institute of Industrial Science and Technology
- Keio University
- Japanese Circulation Society
- Japan Society for the Promotion of Science