A patterned human primitive heart organoid model generated by pluripotent stem cell self-organization.

Autor: Volmert B; Institute for Quantitative Health Science and Engineering, Division of Developmental and Stem Cell Biology, Michigan State University, East Lansing, MI, USA.; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA., Kiselev A; Institute for Quantitative Health Science and Engineering, Division of Developmental and Stem Cell Biology, Michigan State University, East Lansing, MI, USA.; Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, East Lansing, MI, USA.; Division of Dermatology, Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI, 48824, USA., Juhong A; Institute for Quantitative Health Science and Engineering, Division of Biomedical Devices, Michigan State University, East Lansing, MI, USA.; Department of Electrical and Computer Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA., Wang F; Department of Biomedical Engineering, Washington University in Saint Louis, Saint Louis, MO, USA., Riggs A; Institute for Quantitative Health Science and Engineering, Division of Developmental and Stem Cell Biology, Michigan State University, East Lansing, MI, USA.; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA., Kostina A; Institute for Quantitative Health Science and Engineering, Division of Developmental and Stem Cell Biology, Michigan State University, East Lansing, MI, USA.; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA., O'Hern C; Institute for Quantitative Health Science and Engineering, Division of Developmental and Stem Cell Biology, Michigan State University, East Lansing, MI, USA.; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA., Muniyandi P; Institute for Quantitative Health Science and Engineering, Division of Developmental and Stem Cell Biology, Michigan State University, East Lansing, MI, USA.; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA., Wasserman A; Institute for Quantitative Health Science and Engineering, Division of Developmental and Stem Cell Biology, Michigan State University, East Lansing, MI, USA.; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA., Huang A; Institute for Quantitative Health Science and Engineering, Division of Developmental and Stem Cell Biology, Michigan State University, East Lansing, MI, USA.; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA., Lewis-Israeli Y; Institute for Quantitative Health Science and Engineering, Division of Developmental and Stem Cell Biology, Michigan State University, East Lansing, MI, USA.; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA., Panda V; Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, East Lansing, MI, USA.; Institute for Quantitative Health Science and Engineering, Division of Systems Biology, Michigan State University, East Lansing, MI, USA., Bhattacharya S; Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, East Lansing, MI, USA.; Institute for Quantitative Health Science and Engineering, Division of Systems Biology, Michigan State University, East Lansing, MI, USA., Lauver A; Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, East Lansing, MI, USA., Park S; Institute for Quantitative Health Science and Engineering, Division of Developmental and Stem Cell Biology, Michigan State University, East Lansing, MI, USA.; Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, East Lansing, MI, USA.; Division of Dermatology, Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI, 48824, USA., Qiu Z; Institute for Quantitative Health Science and Engineering, Division of Biomedical Devices, Michigan State University, East Lansing, MI, USA.; Department of Electrical and Computer Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA., Zhou C; Department of Biomedical Engineering, Washington University in Saint Louis, Saint Louis, MO, USA., Aguirre A; Institute for Quantitative Health Science and Engineering, Division of Developmental and Stem Cell Biology, Michigan State University, East Lansing, MI, USA. aaguirre@msu.edu.; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA. aaguirre@msu.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Dec 12; Vol. 14 (1), pp. 8245. Date of Electronic Publication: 2023 Dec 12.
DOI: 10.1038/s41467-023-43999-1
Abstrakt: Pluripotent stem cell-derived organoids can recapitulate significant features of organ development in vitro. We hypothesized that creating human heart organoids by mimicking aspects of in utero gestation (e.g., addition of metabolic and hormonal factors) would lead to higher physiological and anatomical relevance. We find that heart organoids produced using this self-organization-driven developmental induction strategy are remarkably similar transcriptionally and morphologically to age-matched human embryonic hearts. We also show that they recapitulate several aspects of cardiac development, including large atrial and ventricular chambers, proepicardial organ formation, and retinoic acid-mediated anterior-posterior patterning, mimicking the developmental processes found in the post-heart tube stage primitive heart. Moreover, we provide proof-of-concept demonstration of the value of this system for disease modeling by exploring the effects of ondansetron, a drug administered to pregnant women and associated with congenital heart defects. These findings constitute a significant technical advance for synthetic heart development and provide a powerful tool for cardiac disease modeling.
(© 2023. The Author(s).)
Databáze: MEDLINE
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