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

Brett Volmert, Artem Kiselev, Aniwat Juhong, Fei Wang, Ashlin Riggs, Aleksandra Kostina, Colin O’Hern, Priyadharshni Muniyandi, Aaron Wasserman, Amanda Huang, Yonatan Lewis-Israeli, Vishal Panda, Sudin Bhattacharya, Adam Lauver, Sangbum Park, Zhen Qiu, Chao Zhou and Aitor Aguirre ()
Additional contact information
Brett Volmert: Michigan State University
Artem Kiselev: Michigan State University
Aniwat Juhong: Michigan State University
Fei Wang: Washington University in Saint Louis
Ashlin Riggs: Michigan State University
Aleksandra Kostina: Michigan State University
Colin O’Hern: Michigan State University
Priyadharshni Muniyandi: Michigan State University
Aaron Wasserman: Michigan State University
Amanda Huang: Michigan State University
Yonatan Lewis-Israeli: Michigan State University
Vishal Panda: Michigan State University
Sudin Bhattacharya: Michigan State University
Adam Lauver: Michigan State University
Sangbum Park: Michigan State University
Zhen Qiu: Michigan State University
Chao Zhou: Washington University in Saint Louis
Aitor Aguirre: Michigan State University

Nature Communications, 2023, vol. 14, issue 1, 1-22

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-43999-1

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