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

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…

• H
  Health~Holland

  Award: LSHM17013-H007
• EC
  European Commission

  Awards: 323182, 602423, FP7/2007-2013, 668724, 707404, 2007-2013, FP7/2007
• Z
  ZonMw

  Awards: 024.003.001, 707404, ERCAdG 323182, LSHM17013-H007, 114022504
• MV
  Ministerie van Onderwijs, Cultuur en Wetenschap

  Awards: JTC2016_FP-40-021 ACM-HF, 024.003.001
• NO
  Nederlandse Organisatie voor Wetenschappelijk Onderzoek

  Awards: 024.003.001, ERCAdG 323182, 024.003, 707404, FP7/2007-2013
• LU
  Leids Universitair Medisch Centrum
• H2
  Horizon 2020 Framework Programme
• SF
  Seventh Framework Programme

  Award: 602423
• ER
  European Research Council

  Awards: ERCAdG 323182, ERCAdG 323182 STEMCARDIOVASC
• SF
  Seventh Framework Programme
• H2
  Horizon 2020

  Awards: 707404, 668724