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Long-term engraftment and maturation of autologous iPSC-derived cardiomyocytes in two rhesus macaques.
Lin, Yongshun; Sato, Noriko; Hong, Sogun; Nakamura, Kenta; Ferrante, Elisa A; Yu, Zu Xi; Chen, Marcus Y; Nakamura, Daisy S; Yang, Xiulan; Clevenger, Randall R; Hunt, Timothy J; Taylor, Joni L; Jeffries, Kenneth R; Keeran, Karen J; Neidig, Lauren E; Mehta, Atul; Schwartzbeck, Robin; Yu, Shiqin Judy; Kelly, Conor; Navarengom, Keron; Takeda, Kazuyo; Adler, Stephen S; Choyke, Peter L; Zou, Jizhong; Murry, Charles E; Boehm, Manfred; Dunbar, Cynthia E.
Affiliation
  • 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, U
  • 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.
Cell Stem Cell ; 31(7): 974-988.e5, 2024 Jul 05.
Article in En | MEDLINE | ID: mdl-38843830
ABSTRACT
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Myocytes, Cardiac / Induced Pluripotent Stem Cells / Macaca mulatta Limits: Animals / Humans Language: En Journal: Cell Stem Cell Year: 2024 Document type: Article Affiliation country: United States
Fulltext
Add to My VHL
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Myocytes, Cardiac / Induced Pluripotent Stem Cells / Macaca mulatta Limits: Animals / Humans Language: En Journal: Cell Stem Cell Year: 2024 Document type: Article Affiliation country: United States