TY - JOUR
T1 - Enhancement of human iPSC-derived cardiomyocyte maturation by chemical conditioning in a 3D environment
AU - Huang, Chen Yu
AU - Peres Moreno Maia-Joca, Rebeca
AU - Ong, Chin Siang
AU - Wilson, Ijala
AU - DiSilvestre, Deborah
AU - Tomaselli, Gordon F.
AU - Reich, Daniel H.
N1 - Funding Information:
This research was supported in part by the Maryland Stem Cell Research Fund (2016-MSCRFI-2735), the Zegar Family Foundation, and the Magic that Matters Fund. Confocal microscopy was carried out at the Johns Hopkins University School of Medicine's Microscope Facility, which is supported by NIH grant S10OD-016374. Flow cytometry experiments were performed at the Homewood Flow Cytometry Resource in the Johns Hopkins University Integrated Imaging Center, which is supported by the Johns Hopkins Whiting School of Engineering and Krieger School of Arts & Sciences. We thank Michael Delannoy and Barbara Smith for assistance in TEM sample preparation and visualization, Hanhvy Buialist for assistance in flow cytometry analysis and Prasenjit Bose for his assistance in force analysis. C.Y.H. acknowledges support from the Ministry of Science of Technology of Taiwan's Postdoctoral Research Abroad Program via Grant Number 105-2917-I-564-003-A1 and American Heart Association fellowship 19POST34380424.
Funding Information:
This research was supported in part by the Maryland Stem Cell Research Fund ( 2016-MSCRFI-2735 ), the Zegar Family Foundation , and the Magic that Matters Fund . Confocal microscopy was carried out at the Johns Hopkins University School of Medicine's Microscope Facility, which is supported by NIH grant S10OD-016374 . Flow cytometry experiments were performed at the Homewood Flow Cytometry Resource in the Johns Hopkins University Integrated Imaging Center, which is supported by the Johns Hopkins Whiting School of Engineering and Krieger School of Arts & Sciences . We thank Michael Delannoy and Barbara Smith for assistance in TEM sample preparation and visualization, Hanhvy Buialist for assistance in flow cytometry analysis and Prasenjit Bose for his assistance in force analysis. C.Y.H. acknowledges support from the Ministry of Science of Technology of Taiwan's Postdoctoral Research Abroad Program via Grant Number 105-2917-I-564-003-A1 and American Heart Association fellowship 19POST34380424 . Appendix A
Publisher Copyright:
© 2019
PY - 2020/1
Y1 - 2020/1
N2 - Recent advances in the understanding and use of pluripotent stem cells have produced major changes in approaches to the diagnosis and treatment of human disease. An obstacle to the use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for regenerative medicine, disease modeling and drug discovery is their immature state relative to adult myocardium. We show the effects of a combination of biochemical factors, thyroid hormone, dexamethasone, and insulin-like growth factor-1 (TDI) on the maturation of hiPSC-CMs in 3D cardiac microtissues (CMTs) that recapitulate aspects of the native myocardium. Based on a comparison of the gene expression profiles and the structural, ultrastructural, and electrophysiological properties of hiPSC-CMs in monolayers and CMTs, and measurements of the mechanical and pharmacological properties of CMTs, we find that TDI treatment in a 3D tissue context yields a higher fidelity adult cardiac phenotype, including sarcoplasmic reticulum function and contractile properties consistent with promotion of the maturation of hiPSC derived cardiomyocytes.
AB - Recent advances in the understanding and use of pluripotent stem cells have produced major changes in approaches to the diagnosis and treatment of human disease. An obstacle to the use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for regenerative medicine, disease modeling and drug discovery is their immature state relative to adult myocardium. We show the effects of a combination of biochemical factors, thyroid hormone, dexamethasone, and insulin-like growth factor-1 (TDI) on the maturation of hiPSC-CMs in 3D cardiac microtissues (CMTs) that recapitulate aspects of the native myocardium. Based on a comparison of the gene expression profiles and the structural, ultrastructural, and electrophysiological properties of hiPSC-CMs in monolayers and CMTs, and measurements of the mechanical and pharmacological properties of CMTs, we find that TDI treatment in a 3D tissue context yields a higher fidelity adult cardiac phenotype, including sarcoplasmic reticulum function and contractile properties consistent with promotion of the maturation of hiPSC derived cardiomyocytes.
KW - 3D cardiac microtissues
KW - Contractile function
KW - Electrophysiology
KW - Induced pluripotent stem cells
KW - Maturation
KW - TDI
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U2 - 10.1016/j.yjmcc.2019.10.001
DO - 10.1016/j.yjmcc.2019.10.001
M3 - Article
C2 - 31655038
AN - SCOPUS:85074533716
SN - 0022-2828
VL - 138
SP - 1
EP - 11
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
ER -
