Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques.

Autor:	Lin Y; iPSC Core, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA., Sato N; Laboratory of Cellular Therapeutics, Molecular Imaging Branch, National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA., Hong S; Translational Stem Cell Biology Branch, NHLBI, NIH, Bethesda, MD 20892, USA., Nakamura K; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA; Department of Medicine/Cardiology, University of Washington, Seattle, WA 98195, USA., Ferrante EA; Translational Vascular Medicine Branch, NHLBI, NIH, Bethesda, MD 20892, USA., Yu ZX; Pathology Core, NHLBI, NIH, Bethesda, MD 20892, USA., Chen MY; Cardiovascular Branch, NHLBI, NIH, Bethesda, MD 20892, USA., Nakamura DS; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA; Department of Medicine/Cardiology, University of Washington, Seattle, WA 98195, USA., Yang X; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA., Clevenger RR; Animal Surgery and Resources Core, NHLBI, NIH, Bethesda, MD 20892, USA., Hunt TJ; Animal Surgery and Resources Core, NHLBI, NIH, Bethesda, MD 20892, USA., Taylor JL; Animal Surgery and Resources Core, NHLBI, NIH, Bethesda, MD 20892, USA., Jeffries KR; Animal Surgery and Resources Core, NHLBI, NIH, Bethesda, MD 20892, USA., Keeran KJ; Animal Surgery and Resources Core, NHLBI, NIH, Bethesda, MD 20892, USA., Neidig LE; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA; Department of Comparative Medicine, University of Washington, Seattle, WA 98195, USA., Mehta A; Translational Vascular Medicine Branch, NHLBI, NIH, Bethesda, MD 20892, USA., Schwartzbeck R; Translational Vascular Medicine Branch, NHLBI, NIH, Bethesda, MD 20892, USA., Yu SJ; Translational Stem Cell Biology Branch, NHLBI, NIH, Bethesda, MD 20892, USA., Kelly C; Translational Stem Cell Biology Branch, NHLBI, NIH, Bethesda, MD 20892, USA., Navarengom K; Translational Vascular Medicine Branch, NHLBI, NIH, Bethesda, MD 20892, USA., Takeda K; Microscopy and Imaging Core, CBER, FDA, Silver Spring, MD, USA., Adler SS; Clinical Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA., Choyke PL; Laboratory of Cellular Therapeutics, Molecular Imaging Branch, National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA., Zou J; iPSC Core, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA., Murry CE; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA; Department of Medicine/Cardiology, University of Washington, Seattle, WA 98195, USA; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA; Department of Bioengineering, University of Washington School of Medicine, Seattle, WA 98195, USA. Electronic address: murry@uw.edu., Boehm M; Translational Vascular Medicine Branch, NHLBI, NIH, Bethesda, MD 20892, USA. Electronic address: boehmm@nhlbi.nih.gov., Dunbar CE; Translational Stem Cell Biology Branch, NHLBI, NIH, Bethesda, MD 20892, USA. Electronic address: dunbarc@nhlbi.nih.gov.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2024 Jul 05; Vol. 31 (7), pp. 974-988.e5. Date of Electronic Publication: 2024 Jun 05.
DOI:	10.1016/j.stem.2024.05.005
Abstrakt:	Cellular therapies with cardiomyocytes produced from induced pluripotent stem cells (iPSC-CMs) offer a potential route to cardiac regeneration as a treatment for chronic ischemic heart disease. Here, we report successful long-term engraftment and in vivo maturation of autologous iPSC-CMs in two rhesus macaques with small, subclinical chronic myocardial infarctions, all without immunosuppression. Longitudinal positron emission tomography imaging using the sodium/iodide symporter (NIS) reporter gene revealed stable grafts for over 6 and 12 months, with no teratoma formation. Histological analyses suggested capability of the transplanted iPSC-CMs to mature and integrate with endogenous myocardium, with no sign of immune cell infiltration or rejection. By contrast, allogeneic iPSC-CMs were rejected within 8 weeks of transplantation. This study provides the longest-term safety and maturation data to date in any large animal model, addresses concerns regarding neoantigen immunoreactivity of autologous iPSC therapies, and suggests that autologous iPSC-CMs would similarly engraft and mature in human hearts. Competing Interests: Declaration of interests Some of these experiments were performed while D.S.N. and C.E.M. were employees of, and K. Nakamura was an advisor to, Sana Biotechnology. D.S.N. and C.E.M. are equity holders in Sana Biotechnology. (Published by Elsevier Inc.)
Databáze:	MEDLINE
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