TY - JOUR
T1 - Three-dimensional filamentous human diseased cardiac tissue model
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.
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
UR - http://www.scopus.com/inward/record.url?scp=84890223557&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2013.10.052
DO - 10.1016/j.biomaterials.2013.10.052
M3 - Article
C2 - 24268663
AN - SCOPUS:84890223557
SN - 0142-9612
VL - 35
SP - 1367
EP - 1377
JO - Biomaterials
JF - Biomaterials
IS - 5
ER -