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
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.
