Generation of mature compact ventricular cardiomyocytes from human pluripotent stem cells.

Animals Cell Culture Techniques / methods Cell Differentiation Cell Line Cell Proliferation Disease Models, Animal Embryo, Mammalian Embryonic Development / physiology Heart Atria / cytology Heart Failure / pathology Heart Ventricles / cytology Humans Myocardial Infarction / complications Myocytes, Cardiac / physiology Pluripotent Stem Cells / physiology Rats

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
26 05 2021
Historique:
received: 16 06 2020
accepted: 18 04 2021
entrez: 27 5 2021
pubmed: 28 5 2021
medline: 10 6 2021
Statut: epublish

Résumé

Compact cardiomyocytes that make up the ventricular wall of the adult heart represent an important therapeutic target population for modeling and treating cardiovascular diseases. Here, we established a differentiation strategy that promotes the specification, proliferation and maturation of compact ventricular cardiomyocytes from human pluripotent stem cells (hPSCs). The cardiomyocytes generated under these conditions display the ability to use fatty acids as an energy source, a high mitochondrial mass, well-defined sarcomere structures and enhanced contraction force. These ventricular cells undergo metabolic changes indicative of those associated with heart failure when challenged in vitro with pathological stimuli and were found to generate grafts consisting of more mature cells than those derived from immature cardiomyocytes following transplantation into infarcted rat hearts. hPSC-derived atrial cardiomyocytes also responded to the maturation cues identified in this study, indicating that the approach is broadly applicable to different subtypes of the heart. Collectively, these findings highlight the power of recapitulating key aspects of embryonic and postnatal development for generating therapeutically relevant cell types from hPSCs.

Identifiants

DOI: 10.1038/s41467-021-23329-z PMID: 34039977 PMC: PMC8155185
pubmed: 34039977
doi: 10.1038/s41467-021-23329-z
pii: 10.1038/s41467-021-23329-z
pmc: PMC8155185
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3155

Subventions

Organisme : CIHR
ID : FDN159937
Pays : Canada

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Auteurs

Shunsuke Funakoshi (S)

McEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.

Ian Fernandes (I)

McEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.

Olya Mastikhina (O)

Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.

Dan Wilkinson (D)

BlueRock Therapeutics, New York, NY, USA.

Thinh Tran (T)

Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.

Wahiba Dhahri (W)

McEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.

Amine Mazine (A)

McEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.
Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.

Donghe Yang (D)

McEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.

Benjamin Burnett (B)

BlueRock Therapeutics, New York, NY, USA.

Jeehoon Lee (J)

BlueRock Therapeutics, New York, NY, USA.

Stephanie Protze (S)

McEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.
Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.

Gary D Bader (GD)

Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Department of Computer Science, University of Toronto, Toronto, ON, Canada.
The Donnelly Centre, University of Toronto, Toronto, ON, Canada.
ORCID: 0000-0003-0185-8861

Sara S Nunes (SS)

Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
Laboratory of Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Heart & Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, ON, Canada.
ORCID: 0000-0003-0906-7204

Michael Laflamme (M)

McEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.
Laboratory of Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada.

Gordon Keller (G)

McEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada. gordon.keller@uhnresearch.ca.
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada. gordon.keller@uhnresearch.ca.
ORCID: 0000-0001-9309-9297

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Generation of mature compact ventricular...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de culture cellulaire › Generation of mature compact ventricular...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › Generation of mature compact ventricular...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Generation of mature compact ventricular...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Generation of mature compact ventricular...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Generation of mature compact ventricular...
questionsmedicales.fr › Structures de l'embryon › Embryon de mammifère › Generation of mature compact ventricular...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Reproduction › Développement embryonnaire et foetal › Développement embryonnaire › Generation of mature compact ventricular...
questionsmedicales.fr › Système cardiovasculaire › Coeur › Atrium du coeur › Generation of mature compact ventricular...
questionsmedicales.fr › Maladies cardiovasculaires › Cardiopathies › Défaillance cardiaque › Generation of mature compact ventricular...
questionsmedicales.fr › Système cardiovasculaire › Coeur › Ventricules cardiaques › Generation of mature compact ventricular...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Generation of mature compact ventricular...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Nécrose › Infarctus › Infarctus du myocarde › Generation of mature compact ventricular...
questionsmedicales.fr › Cellules › Cellules musculaires › Myocytes cardiaques › Generation of mature compact ventricular...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches pluripotentes › Generation of mature compact ventricular...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Generation of mature compact ventricular...