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 (+2 others)
2019 Stem Cell Reports  
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
more » ... ripotent 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.
doi:10.1016/j.stemcr.2019.05.024 pmid:31231023 pmcid:PMC6626888 fatcat:b5hmzvroh5ez5fe27abdl5eo2y