Medical College of Wisconsin
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A Platform for Generation of Chamber-Specific Cardiac Tissues and Disease Modeling. Cell 2019 Feb 07;176(4):913-927.e18

Date

01/29/2019

Pubmed ID

30686581

Pubmed Central ID

PMC6456036

DOI

10.1016/j.cell.2018.11.042

Scopus ID

2-s2.0-85061001208 (requires institutional sign-in at Scopus site)   498 Citations

Abstract

Tissue engineering using cardiomyocytes derived from human pluripotent stem cells holds a promise to revolutionize drug discovery, but only if limitations related to cardiac chamber specification and platform versatility can be overcome. We describe here a scalable tissue-cultivation platform that is cell source agnostic and enables drug testing under electrical pacing. The plastic platform enabled on-line noninvasive recording of passive tension, active force, contractile dynamics, and Ca2+ transients, as well as endpoint assessments of action potentials and conduction velocity. By combining directed cell differentiation with electrical field conditioning, we engineered electrophysiologically distinct atrial and ventricular tissues with chamber-specific drug responses and gene expression. We report, for the first time, engineering of heteropolar cardiac tissues containing distinct atrial and ventricular ends, and we demonstrate their spatially confined responses to serotonin and ranolazine. Uniquely, electrical conditioning for up to 8 months enabled modeling of polygenic left ventricular hypertrophy starting from patient cells.

Author List

Zhao Y, Rafatian N, Feric NT, Cox BJ, Aschar-Sobbi R, Wang EY, Aggarwal P, Zhang B, Conant G, Ronaldson-Bouchard K, Pahnke A, Protze S, Lee JH, Davenport Huyer L, Jekic D, Wickeler A, Naguib HE, Keller GM, Vunjak-Novakovic G, Broeckel U, Backx PH, Radisic M

Author

Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Action Potentials
Cell Differentiation
Cells, Cultured
Electrophysiological Phenomena
Humans
Induced Pluripotent Stem Cells
Models, Biological
Myocardium
Myocytes, Cardiac
Pluripotent Stem Cells
Tissue Culture Techniques
Tissue Engineering