Coculture with noncardiac cells promoted maturation of human stem cell–derived cardiomyocyte microtissues. Issue 10 (14th May 2019)

• Record Type: Journal Article
• Authors: Varzideh, Fahimeh; Mahmoudi, Elena; Pahlavan, Sara
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 10(2019)
• Page Start: 16681
• Page End: 16691
• Publication Date: 2019-05-14
• Subjects: cardiac progenitor cell -- endothelial cell -- maturation -- microtissue -- mesenchymal stem cell; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.28926
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Cardiomyocytes derived from human pluripotent stem cells (hPSC‐CM) provided a promising cell source for cell therapy, drug screening, and disease modeling. However, hPSC‐CM are immature and phenotypically more similar to fetal rather than adult cardiomyocytes in vitro . We explored the impact of coculture of human embryonic stem cell–derived mesenchymal stem cells (hESC‐MSC) and endothelial cells (ECs) with human embryonic stem cells–derived cardiac progenitor cells (hESC‐CPC) on the gene expression and electrophysiological properties of hESC‐CPC in 3D culture (microtissue spheroid). In this regard, hESC‐CPC were cultured either alone (CM microtissue) or in coculture with EC and hESC‐MSC (CMEM microtissue) on agar‐coated 96‐well round‐bottomed plates for 1 week. Lumen‐like structures were formed in CMEM but not in CM microtissue. Cardiac progenitor markers ( TBX5, GATA4 ) were downregulated and cardiac sarcomeric transcripts ( MLC2v and β‐MHC ) were upregulated in CMEM compared with CM microtissue. Furthermore, beating frequencies, beating cycles, and field potential durations of CMEM resided in the range of adult cardiomyocytes rather than fetal like phenotypes observed in CM microtissue. These findings demonstrated that CPC spheroids in coculture with EC and hESC‐MSC may undergo greater maturation toward an adult‐like cardiomyocyte. Abstract : This study aims to investigate the effect of endothelial cells (ECs) and human embryonic stem cells–derived mesenchymal stem cells (hESC‐MSC) on gene expression and electrophysiological properties of cardiomyocytes in three‐dimensional culture. We formed cardiac microtissue on agar‐coated round bottom 96‐well plates (scaffold‐free). Our results showed that cardiac microtissue derived from EC, hESC‐MSCs and hESC‐CPCs enhanced gene expression and electrophysiological function of cardiomyocytes