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Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts.
Chong, James J H; Yang, Xiulan; Don, Creighton W; Minami, Elina; Liu, Yen-Wen; Weyers, Jill J; Mahoney, William M; Van Biber, Benjamin; Cook, Savannah M; Palpant, Nathan J; Gantz, Jay A; Fugate, James A; Muskheli, Veronica; Gough, G Michael; Vogel, Keith W; Astley, Cliff A; Hotchkiss, Charlotte E; Baldessari, Audrey; Pabon, Lil; Reinecke, Hans; Gill, Edward A; Nelson, Veronica; Kiem, Hans-Peter; Laflamme, Michael A; Murry, Charles E.
Afiliación
  • Chong JJ; 1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Cardiology Westmead Hospital, Westmead, New South Wales 2145, Australia [4]
  • Yang X; 1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
  • Don CW; Department of Medicine/Cardiology, University of Washington, Seattle, Washington 98195, USA.
  • Minami E; 1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA [4] Dep
  • Liu YW; 1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
  • Weyers JJ; 1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
  • Mahoney WM; 1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
  • Van Biber B; 1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
  • Cook SM; Department of Comparative Medicine, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA.
  • Palpant NJ; 1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
  • Gantz JA; 1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA [4] Dep
  • Fugate JA; 1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
  • Muskheli V; 1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
  • Gough GM; Washington National Primate Research Center, University of Washington, Seattle, Washington 98195, USA.
  • Vogel KW; Washington National Primate Research Center, University of Washington, Seattle, Washington 98195, USA.
  • Astley CA; Washington National Primate Research Center, University of Washington, Seattle, Washington 98195, USA.
  • Hotchkiss CE; Washington National Primate Research Center, University of Washington, Seattle, Washington 98195, USA.
  • Baldessari A; Washington National Primate Research Center, University of Washington, Seattle, Washington 98195, USA.
  • Pabon L; 1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
  • Reinecke H; 1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
  • Gill EA; Department of Medicine/Cardiology, University of Washington, Seattle, Washington 98195, USA.
  • Nelson V; Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
  • Kiem HP; 1] Department of Pathology, University of Washington, Seattle, Washington 98195, USA [2] Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
  • Laflamme MA; 1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
  • Murry CE; 1] Center for Cardiovascular Biology, University of Washington, Seattle, Washington 98109, USA [2] Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA [3] Department of Pathology, University of Washington, Seattle, Washington 98195, USA [4] Dep
Nature ; 510(7504): 273-7, 2014 Jun 12.
Article en En | MEDLINE | ID: mdl-24776797
ABSTRACT
Pluripotent stem cells provide a potential solution to current epidemic rates of heart failure by providing human cardiomyocytes to support heart regeneration. Studies of human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) in small-animal models have shown favourable effects of this treatment. However, it remains unknown whether clinical-scale hESC-CM transplantation is feasible, safe or can provide sufficient myocardial regeneration. Here we show that hESC-CMs can be produced at a clinical scale (more than one billion cells per batch) and cryopreserved with good viability. Using a non-human primate model of myocardial ischaemia followed by reperfusion, we show that cryopreservation and intra-myocardial delivery of one billion hESC-CMs generates extensive remuscularization of the infarcted heart. The hESC-CMs showed progressive but incomplete maturation over a 3-month period. Grafts were perfused by host vasculature, and electromechanical junctions between graft and host myocytes were present within 2 weeks of engraftment. Importantly, grafts showed regular calcium transients that were synchronized to the host electrocardiogram, indicating electromechanical coupling. In contrast to small-animal models, non-fatal ventricular arrhythmias were observed in hESC-CM-engrafted primates. Thus, hESC-CMs can remuscularize substantial amounts of the infarcted monkey heart. Comparable remuscularization of a human heart should be possible, but potential arrhythmic complications need to be overcome.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Regeneración / Miocitos Cardíacos / Células Madre Embrionarias / Corazón / Infarto del Miocardio Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Nature Año: 2014 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Regeneración / Miocitos Cardíacos / Células Madre Embrionarias / Corazón / Infarto del Miocardio Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Nature Año: 2014 Tipo del documento: Article