A New Versatile Platform for Assessment of Improved Cardiac Performance in Human-Engineered Heart Tissues

Marcelo C. Ribeiro, Jose M. Rivera-Arbelaez, Carla Cofino-Fabres, Verena Schwach, Rolf H. Slaats, Simone A. ten Den, Kim Vermeul, Albert van den Berg, Jose M. Perez-Pomares, Loes I. Segerink, Juan A. Guadix, Robert Passier*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
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Abstract

Cardiomyocytes derived from human pluripotent stem cells (hPSC-CMs) hold a great potential as human in vitro models for studying heart disease and for drug safety screening. Nevertheless, their associated immaturity relative to the adult myocardium limits their utility in cardiac research. In this study, we describe the development of a platform for generating three-dimensional engineered heart tissues (EHTs) from hPSC-CMs for the measurement of force while under mechanical and electrical stimulation. The modular and versatile EHT platform presented here allows for the formation of three tissues per well in a 12-well plate format, resulting in 36 tissues per plate. We compared the functional performance of EHTs and their histology in three different media and demonstrated that tissues cultured and maintained in maturation medium, containing triiodothyronine (T3), dexamethasone, and insulin-like growth factor-1 (TDI), resulted in a higher force of contraction, sarcomeric organization and alignment, and a higher and lower inotropic response to isoproterenol and nifedipine, respectively. Moreover, in this study, we highlight the importance of integrating a serum-free maturation medium in the EHT platform, making it a suitable tool for cardiovascular research, disease modeling, and preclinical drug testing
Original languageEnglish
Article number214
JournalJournal of Personalized Medicine
Volume12
Issue number2
DOIs
Publication statusPublished - 4 Feb 2022

Keywords

  • versatile platform
  • engineered heart tissues
  • serum-free
  • contractile force
  • cardiac performance
  • hPSC-CMs

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