Modelling cardiac fibrosis using three-dimensional cardiac microtissues derived from human embryonic stem cells

Journal of Biological Engineering
Mi-Ok LeeMi-Young Son

Abstract

Cardiac fibrosis is the most common pathway of many cardiac diseases. To date, there has been no suitable in vitro cardiac fibrosis model that could sufficiently mimic the complex environment of the human heart. Here, a three-dimensional (3D) cardiac sphere platform of contractile cardiac microtissue, composed of human embryonic stem cell (hESC)-derived cardiomyocytes (CMs) and mesenchymal stem cells (MSCs), is presented to better recapitulate the human heart. We hypothesized that MSCs would develop an in vitro fibrotic reaction in response to treatment with transforming growth factor-β1 (TGF-β1), a primary inducer of cardiac fibrosis. The addition of MSCs improved sarcomeric organization, electrophysiological properties, and the expression of cardiac-specific genes, suggesting their physiological relevance in the generation of human cardiac microtissue model in vitro. MSCs could also generate fibroblasts within 3D cardiac microtissues and, subsequently, these fibroblasts were transdifferentiated into myofibroblasts by the exogenous addition of TGF-β1. Cardiac microtissues displayed fibrotic features such as the deposition of collagen, the presence of numerous apoptotic CMs and the dissolution of mitochondrial networks. Further...Continue Reading

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Citations

Jul 1, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ye Seul SonMi-Young Son
Mar 3, 2020·Frontiers in Molecular Biosciences·Philippe BeauchampChristian Zuppinger
Jul 17, 2020·Frontiers in Bioengineering and Biotechnology·Sneha GopalJonathan S Dordick
Jul 12, 2019·Frontiers in Cardiovascular Medicine·Christian Zuppinger
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Jeongmin HaJanghwan Kim
Jan 22, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Chi Keung Lam, Joseph C Wu
Feb 16, 2021·Journal of the American Heart Association·Caitlin HallDavor Pavlovic
Mar 19, 2021·Circulation Research·Giulia CampostriniChristine L Mummery
Jun 9, 2021·Cellular and Molecular Life Sciences : CMLS·David DolivoThomas Mustoe
Jul 16, 2021·Frontiers in Cell and Developmental Biology·Eric K N GähwilerMaximilian Y Emmert
Jul 27, 2021·Frontiers in Physiology·Giorgia PalanoErik Müllers
Sep 26, 2020·ACS Biomaterials Science & Engineering·LaTonya R Simon, Kristyn S Masters
Oct 12, 2021·Advanced Healthcare Materials·Xin LiuQi Gu
Apr 1, 2021·Stem Cells·Kayla SoonSara S Nunes

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Methods Mentioned

BETA
FACS
flow cytometry
bioprinting
chip

Software Mentioned

MultiExperiment Viewer
MSigDB
Axion Cardiac Data Plotting Tool
GSEA
Image J
Cytoscape
Reactome FI
FlowJo
GraphPad
Axion BioSystems ’ Integrated Studio ( AxIS )

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Apoptosis

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