Engineered Macroscale Cardiac Constructs Elicit Human Myocardial Tissue-like Functionality

Maria Valls-Margarit, Olalla Iglesias-García, Claudia Di Guglielmo, Leonardo Sarlabous, Karine Tadevosyan, Roberto Paoli, Jordi Comelles, Dolores Blanco-Almazán, Senda Jiménez-Delgado, Oscar Castillo-Fernández, Josep Samitier, Raimon Jané, Elena Martínez, Ángel Raya

    Research output: Contribution to journalArticleResearch

    19 Citations (Scopus)

    Abstract

    © 2019 The Authors In vitro surrogate models of human cardiac tissue hold great promise in disease modeling, cardiotoxicity testing, and future applications in regenerative medicine. However, the generation of engineered human cardiac constructs with tissue-like functionality is currently thwarted by difficulties in achieving efficient maturation at the cellular and/or tissular level. Here, we report on the design and implementation of a platform for the production of engineered cardiac macrotissues from human pluripotent stem cells (PSCs), which we term “CardioSlice.” PSC-derived cardiomyocytes, together with human fibroblasts, are seeded into large 3D porous scaffolds and cultured using a parallelized perfusion bioreactor with custom-made culture chambers. Continuous electrical stimulation for 2 weeks promotes cardiomyocyte alignment and synchronization, and the emergence of cardiac tissue-like properties. These include electrocardiogram-like signals that can be readily measured on the surface of CardioSlice constructs, and a response to proarrhythmic drugs that is predictive of their effect in human patients. In this article, Raya and colleagues design and implement a cardiac tissue-engineering platform for the production of macrotissues from human pluripotent stem cells. These human cardiac macrotissues can be electrically stimulated, and their electric activity recorded from the surface of the constructs. After 2 weeks of electrical stimulation, distinct cardiac tissue-like properties appear such as electrocardiogram-like signals and patient-like response to cardiotoxic drugs.
    Original languageEnglish
    Pages (from-to)207-220
    JournalStem Cell Reports
    Volume13
    DOIs
    Publication statusPublished - 9 Jul 2019

    Keywords

    • cardiac tissue engineering
    • CardioSlice
    • ECG-like signals
    • electrical stimulation
    • heart physiology
    • human induced pluripotent stem cells
    • perfusion bioreactor
    • tissue-like properties

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