Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease.

Human-iPSC-Derived Cardiac Stromal Cells Enhance Maturation in 3D Cardiac Microtissues and Reveal Non-cardiomyocyte Contributions to Heart Disease. Cell Stem Cell. 2020 May 20;: Authors: Giacomelli E, Meraviglia V, Campostrini G, Cochrane A, Cao X, van Helden RWJ, Krotenberg Garcia A, Mircea M, Kostidis S, Davis RP, van Meer BJ, Jost CR, Koster AJ, Mei H, Míguez DG, Mulder AA, Ledesma-Terrón M, Pompilio G, Sala L, Salvatori DCF, Slieker RC, Sommariva E, de Vries AAF, Giera M, Semrau S, Tertoolen LGJ, Orlova VV, Bellin M, Mummery CL Abstract Cardiomyocytes (CMs) from human induced pluripotent stem cells (hiPSCs) are functionally immature, but this is improved by incorporation into engineered tissues or forced contraction. Here, we showed that tri-cellular combinations of hiPSC-derived CMs, cardiac fibroblasts (CFs), and cardiac endothelial cells also enhance maturation in easily constructed, scaffold-free, three-dimensional microtissues (MTs). hiPSC-CMs in MTs with CFs showed improved sarcomeric structures with T-tubules, enhanced contractility, and mitochondrial respiration and were electrophysiologically more mature than MTs without CFs. Interactions mediating maturation included coupling between hiPSC-CMs and CFs through connexin 43 (CX43) gap junctions and increased intracellular cyclic AMP (cAMP). Scaled production of thousands of hiPSC-MTs was highly reproducible across lines and differentiated cell batches. MTs containing hea...
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research