Macrophages enhance contractile force in iPSC-derived human engineered cardiac tissue

Roberta I. Lock; Pamela L. Graney; Daniel Naveed Tavakol; Trevor R. Nash; Youngbin Kim; Eloy Sanchez, Jr.; Margaretha Morsink; Derek Ning; Connie Chen; Sharon Fleischer; Ilaria Baldassarri; Gordana Vunjak-Novakovic

Cell Reports (Jun 2024)

Macrophages enhance contractile force in iPSC-derived human engineered cardiac tissue

Roberta I. Lock,
Pamela L. Graney,
Daniel Naveed Tavakol,
Trevor R. Nash,
Youngbin Kim,
Eloy Sanchez, Jr.,
Margaretha Morsink,
Derek Ning,
Connie Chen,
Sharon Fleischer,
Ilaria Baldassarri,
Gordana Vunjak-Novakovic

Affiliations

Roberta I. Lock: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
Pamela L. Graney: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
Daniel Naveed Tavakol: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
Trevor R. Nash: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
Youngbin Kim: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
Eloy Sanchez, Jr.: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
Margaretha Morsink: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
Derek Ning: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
Connie Chen: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
Sharon Fleischer: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
Ilaria Baldassarri: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA
Gordana Vunjak-Novakovic: Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA; Department of Medicine, Columbia University, New York, NY 10032, USA; College of Dental Medicine, Columbia University, New York, NY 10032, USA; Corresponding author

Journal volume & issue: Vol. 43, no. 6
p. 114302

Abstract

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Summary: Resident cardiac macrophages are critical mediators of cardiac function. Despite their known importance to cardiac electrophysiology and tissue maintenance, there are currently no stem-cell-derived models of human engineered cardiac tissues (hECTs) that include resident macrophages. In this study, we made an induced pluripotent stem cell (iPSC)-derived hECT model with a resident population of macrophages (iM0) to better recapitulate the native myocardium and characterized their impact on tissue function. Macrophage retention within the hECTs was confirmed via immunofluorescence after 28 days of cultivation. The inclusion of iM0s significantly impacted hECT function, increasing contractile force production. A potential mechanism underlying these changes was revealed by the interrogation of calcium signaling, which demonstrated the modulation of β-adrenergic signaling in +iM0 hECTs. Collectively, these findings demonstrate that macrophages significantly enhance cardiac function in iPSC-derived hECT models, emphasizing the need to further explore their contributions not only in healthy hECT models but also in the contexts of disease and injury.

CP: Developmental biology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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