Cardiac ultrastructure inspired matrix induces advanced metabolic and functional maturation of differentiated human cardiomyocytes.

Autor:	Afzal J; Department of Medicine, Division of Cardiology, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: junaid.afzal@ucsf.edu., Liu Y; Department of Biomedical Engineering, University of Connecticut Health, Farmington, CT 06032, USA., Du W; Department of Biomedical Engineering, University of Connecticut Health, Farmington, CT 06032, USA., Suhail Y; Department of Biomedical Engineering, University of Connecticut Health, Farmington, CT 06032, USA; Center for Cellular Analysis and Modeling, University of Connecticut Health, Farmington, CT 06032, USA., Zong P; Department of Cell Biology, University of Connecticut Health, Farmington, CT 06032, USA; Calhoun Cardiology Center, University of Connecticut Health, Farmington, CT 06032, USA., Feng J; Department of Cell Biology, University of Connecticut Health, Farmington, CT 06032, USA; Calhoun Cardiology Center, University of Connecticut Health, Farmington, CT 06032, USA., Ajeti V; Department of Biomedical Engineering, University of Connecticut Health, Farmington, CT 06032, USA; Center for Cellular Analysis and Modeling, University of Connecticut Health, Farmington, CT 06032, USA., Sayyad WA; Department of Cell Biology, Yale University, New Haven, CT 06510, USA., Nikolaus J; West Campus Imaging Core, Yale University, New Haven, CT 06477, USA., Yankova M; Electron Microscopy Core, University of Connecticut Health, Farmington, CT 06032, USA., Deymier AC; Department of Biomedical Engineering, University of Connecticut Health, Farmington, CT 06032, USA., Yue L; Department of Cell Biology, University of Connecticut Health, Farmington, CT 06032, USA; Calhoun Cardiology Center, University of Connecticut Health, Farmington, CT 06032, USA., Kshitiz; Department of Biomedical Engineering, University of Connecticut Health, Farmington, CT 06032, USA; Center for Cellular Analysis and Modeling, University of Connecticut Health, Farmington, CT 06032, USA; Department of Cell Biology, University of Connecticut Health, Farmington, CT 06032, USA. Electronic address: kshitiz@uchc.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Jul 26; Vol. 40 (4), pp. 111146.
DOI:	10.1016/j.celrep.2022.111146
Abstrakt:	The vast potential of human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs) in preclinical models of cardiac pathologies, precision medicine, and drug screening remains to be fully realized because hiPSC-CMs are immature without adult-like characteristics. Here, we present a method to accelerate hiPSC-CM maturation on a substrate, cardiac mimetic matrix (CMM), mimicking adult human heart matrix ligand chemistry, rigidity, and submicron ultrastructure, which synergistically mature hiPSC-CMs rapidly within 30 days. hiPSC-CMs matured on CMM exhibit systemic transcriptomic maturation toward an adult heart state, are aligned with high strain energy, metabolically rely on oxidative phosphorylation and fatty acid oxidation, and display enhanced redox handling capability, efficient calcium handling, and electrophysiological features of ventricular myocytes. Endothelin-1-induced pathological hypertrophy is mitigated on CMM, highlighting the role of a native cardiac microenvironment in withstanding hypertrophy progression. CMM is a convenient model for accelerated development of ventricular myocytes manifesting highly specialized cardiac-specific functions. Competing Interests: Declaration of interests K.K., J.A., W.D., and Y.S. are inventors on a provisional patent filed describing the technology in this paper. K.K. is an inventor of a licensed patent to CuriBio, Inc. (9,994,812), whose products were used for comparative purposes during the review process. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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