2. Academic Validation
  3. Macrophages enhance contractile force in iPSC-derived human engineered cardiac tissue

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

  • Cell Rep. 2024 Jun 25;43(6):114302. doi: 10.1016/j.celrep.2024.114302.
Roberta I Lock 1,  Pamela L Graney 1,  Daniel Naveed Tavakol 1,  Trevor R Nash 1,  Youngbin Kim 1,  Eloy Sanchez Jr 1,  Margaretha Morsink 1,  Derek Ning 1,  Connie Chen 1,  Sharon Fleischer 1,  Ilaria Baldassarri 1,  Gordana Vunjak-Novakovic 2
Affiliations

Affiliations

  • 1 Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
  • 2 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. Electronic address: gv2131@columbia.edu.
PMID: 38824644 DOI: 10.1016/j.celrep.2024.114302
Abstract

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.

Keywords

CP: Developmental biology; cardiac; iPSC; immune; macrophage; myocardium; stem cell; tissue engineering.

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