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

  1. Author:
    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
    Choyke, Peter L
    Zou, Jizhong
    Murry, Charles E
    Boehm, Manfred
    Dunbar, Cynthia E

  2. Author Address

    iPSC Core, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD 20892, USA., Laboratory of Cellular Therapeutics, Molecular Imaging Branch, National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA., Translational Stem Cell Biology Branch, NHLBI, NIH, Bethesda, MD 20892, USA., 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., Translational Vascular Medicine Branch, NHLBI, NIH, Bethesda, MD 20892, USA., Pathology Core, NHLBI, NIH, Bethesda, MD 20892, USA., Cardiovascular Branch, NHLBI, NIH, Bethesda, MD 20892, USA., 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., Animal Surgery and Resources Core, NHLBI, NIH, Bethesda, MD 20892, USA., 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., Microscopy and Imaging Core, CBER, FDA, Silver Spring, MD, USA., Clinical Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA., 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., Translational Vascular Medicine Branch, NHLBI, NIH, Bethesda, MD 20892, USA. Electronic address: boehmm@nhlbi.nih.gov., Translational Stem Cell Biology Branch, NHLBI, NIH, Bethesda, MD 20892, USA. Electronic address: dunbarc@nhlbi.nih.gov.,
    1. Year: 2024
    2. Date: Jul 7
    3. Epub Date: 2024 05 29
  2. Journal: Cell Stem Cell
    1. 31
    2. 7
    3. Pages: 974-988
  4. Type of Article: Article
  1. 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. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.stem.2024.05.005
  3. PMID: 38843830
  4. PMCID: PMC11227404
  5. View record in Web of Science®
  6. WOS: 001269040300001
  7. PII : S1934-5909(24)00182-6

Library Notes

  1. Fiscal Year: FY2023-2024
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