Three-dimensional filamentous human diseased cardiac tissue model

Zhen Ma; Sangmo Koo; Micaela A. Finnegan; Peter Loskill; Nathaniel Huebsch; Natalie C. Marks; Bruce R. Conklin; Costas P. Grigoropoulos; Kevin E. Healy

doi:10.1016/j.biomaterials.2013.10.052

Three-dimensional filamentous human diseased cardiac tissue model

Zhen Ma, Sangmo Koo, Micaela A. Finnegan, Peter Loskill, Nathaniel Huebsch, Natalie C. Marks, Bruce R. Conklin, Costas P. Grigoropoulos, Kevin E. Healy

Research output: Contribution to journal › Article › peer-review

105 Scopus citations

Abstract

A human invitro cardiac tissue model would be a significant advancement for understanding, studying, and developing new strategies for treating cardiac arrhythmias and related cardiovascular diseases. We developed an invitro model of three-dimensional (3D) human cardiac tissue by populating synthetic filamentous matrices with cardiomyocytes derived from healthy wild-type volunteer (WT) and patient-specific long QT syndrome type 3 (LQT3) induced pluripotent stem cells (iPS-CMs) to mimic the condensed and aligned human ventricular myocardium. Using such a highly controllable cardiac model, we studied the contractility malfunctions associated with the electrophysiological consequences of LQT3 and their response to a panel of drugs. By varying the stiffness of filamentous matrices, LQT3 iPS-CMs exhibited different level of contractility abnormality and susceptibility to drug-induced cardiotoxicity.

Original language	English (US)
Pages (from-to)	1367-1377
Number of pages	11
Journal	Biomaterials
Volume	35
Issue number	5
DOIs	https://doi.org/10.1016/j.biomaterials.2013.10.052
State	Published - Feb 2014
Externally published	Yes

Keywords

Cardiac contractility
Cardiac disease model
Drug testing
Induced pluripotent stem cells
Long QT syndrome
Two-photon initiated polymerization

ASJC Scopus subject areas

Biophysics
Bioengineering
Ceramics and Composites
Biomaterials
Mechanics of Materials

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10.1016/j.biomaterials.2013.10.052

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title = "Three-dimensional filamentous human diseased cardiac tissue model",

abstract = "A human invitro cardiac tissue model would be a significant advancement for understanding, studying, and developing new strategies for treating cardiac arrhythmias and related cardiovascular diseases. We developed an invitro model of three-dimensional (3D) human cardiac tissue by populating synthetic filamentous matrices with cardiomyocytes derived from healthy wild-type volunteer (WT) and patient-specific long QT syndrome type 3 (LQT3) induced pluripotent stem cells (iPS-CMs) to mimic the condensed and aligned human ventricular myocardium. Using such a highly controllable cardiac model, we studied the contractility malfunctions associated with the electrophysiological consequences of LQT3 and their response to a panel of drugs. By varying the stiffness of filamentous matrices, LQT3 iPS-CMs exhibited different level of contractility abnormality and susceptibility to drug-induced cardiotoxicity.",

keywords = "Cardiac contractility, Cardiac disease model, Drug testing, Induced pluripotent stem cells, Long QT syndrome, Two-photon initiated polymerization",

author = "Zhen Ma and Sangmo Koo and Finnegan, {Micaela A.} and Peter Loskill and Nathaniel Huebsch and Marks, {Natalie C.} and Conklin, {Bruce R.} and Grigoropoulos, {Costas P.} and Healy, {Kevin E.}",

note = "Funding Information: This work was supported by NIH-NHLBI R01HL096525 , R01HL108677 , U01HL100406 , U01HL098179 and in part by NIH-NCATS UH2TR000487 . Work at the Laser Thermal Laboratory was in part supported by the NSF (DMI-0556363). Z.M. would like to acknowledge Siebel Institute Postdoctoral Fellowship (41523-31595-44-OYZHMA-IQKEH). We acknowledge assistance from the Berkeley Stem Cell Shared Facility and Biological Imaging Facility. ",

year = "2014",

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doi = "10.1016/j.biomaterials.2013.10.052",

language = "English (US)",

volume = "35",

pages = "1367--1377",

journal = "Biomaterials",

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AU - Ma, Zhen

AU - Koo, Sangmo

AU - Finnegan, Micaela A.

AU - Loskill, Peter

AU - Huebsch, Nathaniel

AU - Marks, Natalie C.

AU - Conklin, Bruce R.

AU - Grigoropoulos, Costas P.

AU - Healy, Kevin E.

N1 - Funding Information: This work was supported by NIH-NHLBI R01HL096525 , R01HL108677 , U01HL100406 , U01HL098179 and in part by NIH-NCATS UH2TR000487 . Work at the Laser Thermal Laboratory was in part supported by the NSF (DMI-0556363). Z.M. would like to acknowledge Siebel Institute Postdoctoral Fellowship (41523-31595-44-OYZHMA-IQKEH). We acknowledge assistance from the Berkeley Stem Cell Shared Facility and Biological Imaging Facility.

PY - 2014/2

Y1 - 2014/2

N2 - A human invitro cardiac tissue model would be a significant advancement for understanding, studying, and developing new strategies for treating cardiac arrhythmias and related cardiovascular diseases. We developed an invitro model of three-dimensional (3D) human cardiac tissue by populating synthetic filamentous matrices with cardiomyocytes derived from healthy wild-type volunteer (WT) and patient-specific long QT syndrome type 3 (LQT3) induced pluripotent stem cells (iPS-CMs) to mimic the condensed and aligned human ventricular myocardium. Using such a highly controllable cardiac model, we studied the contractility malfunctions associated with the electrophysiological consequences of LQT3 and their response to a panel of drugs. By varying the stiffness of filamentous matrices, LQT3 iPS-CMs exhibited different level of contractility abnormality and susceptibility to drug-induced cardiotoxicity.

AB - A human invitro cardiac tissue model would be a significant advancement for understanding, studying, and developing new strategies for treating cardiac arrhythmias and related cardiovascular diseases. We developed an invitro model of three-dimensional (3D) human cardiac tissue by populating synthetic filamentous matrices with cardiomyocytes derived from healthy wild-type volunteer (WT) and patient-specific long QT syndrome type 3 (LQT3) induced pluripotent stem cells (iPS-CMs) to mimic the condensed and aligned human ventricular myocardium. Using such a highly controllable cardiac model, we studied the contractility malfunctions associated with the electrophysiological consequences of LQT3 and their response to a panel of drugs. By varying the stiffness of filamentous matrices, LQT3 iPS-CMs exhibited different level of contractility abnormality and susceptibility to drug-induced cardiotoxicity.

KW - Cardiac contractility

KW - Cardiac disease model

KW - Drug testing

KW - Induced pluripotent stem cells

KW - Long QT syndrome

KW - Two-photon initiated polymerization

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Three-dimensional filamentous human diseased cardiac tissue model

Abstract

Keywords

ASJC Scopus subject areas

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