Three-dimensional filamentous human diseased cardiac tissue model.

A human in vitro 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 in vitro 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.

[1]  J. Bechhoefer,et al.  Calibration of atomic‐force microscope tips , 1993 .

[2]  Jong Hwan Sung,et al.  Microtechnology for Mimicking In Vivo Tissue Environment , 2012, Annals of Biomedical Engineering.

[3]  Gregory B. Sands,et al.  Three-dimensional transmural organization of perimysial collagen in the heart , 2008, American journal of physiology. Heart and circulatory physiology.

[4]  Meifeng Xu,et al.  Laser patterning for the study of MSC cardiogenic differentiation at the single-cell level , 2013, Light: Science & Applications.

[5]  B N Chichkov,et al.  Two-photon polymerization-generated and micromolding-replicated 3D scaffolds for peripheral neural tissue engineering applications , 2012, Biofabrication.

[6]  Milica Radisic,et al.  Influence of substrate stiffness on the phenotype of heart cells , 2010, Biotechnology and bioengineering.

[7]  B. Strulovici,et al.  Induced pluripotent stem cells — opportunities for disease modelling and drug discovery , 2011, Nature Reviews Drug Discovery.

[8]  Thomas Boudou,et al.  A Microfabricated Platform to Measure and Manipulate the Mechanics of Engineered Cardiac Microtissues , 2012 .

[9]  Andrew D McCulloch,et al.  Substrate stiffness affects the functional maturation of neonatal rat ventricular myocytes. , 2008, Biophysical journal.

[10]  Christopher W Ward,et al.  X-ROS Signaling: Rapid Mechano-Chemo Transduction in Heart , 2011, Science.

[11]  M. Laflamme,et al.  Methods for the derivation and use of cardiomyocytes from human pluripotent stem cells. , 2011, Methods in molecular biology.

[12]  Costas P. Grigoropoulos,et al.  Measurement of contractile forces generated by individual fibroblasts on self-standing fiber scaffolds , 2010, Biomedical microdevices.

[13]  Kam W Leong,et al.  Pluripotent stem cell-derived cardiac tissue patch with advanced structure and function. , 2011, Biomaterials.

[14]  Karl-Ludwig Laugwitz,et al.  Patient-specific induced pluripotent stem-cell models for long-QT syndrome. , 2010, New England Journal of Medicine.

[15]  P. Galie,et al.  Substrate stiffness affects sarcomere and costamere structure and electrophysiological function of isolated adult cardiomyocytes. , 2013, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[16]  Hirofumi Hidai,et al.  Self-standing aligned fiber scaffold fabrication by two photon photopolymerization , 2009, Biomedical microdevices.

[17]  Lior Gepstein,et al.  Modelling the long QT syndrome with induced pluripotent stem cells , 2011, Nature.

[18]  Milan Mrksich,et al.  Geometric cues for directing the differentiation of mesenchymal stem cells , 2010, Proceedings of the National Academy of Sciences.

[19]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[20]  Mandy B. Esch,et al.  Microfabricated mammalian organ systems and their integration into models of whole animals and humans. , 2013, Lab on a chip.

[21]  Hirofumi Hidai,et al.  The effect of micronscale anisotropic cross patterns on fibroblast migration. , 2010, Biomaterials.

[22]  Chok-Kwan Cheung,et al.  Adaptive motion tracking block matching algorithms for video coding , 1999, IEEE Trans. Circuits Syst. Video Technol..

[23]  Xian-Zi Dong,et al.  Improving spatial resolution and reducing aspect ratio in multiphoton polymerization nanofabrication , 2008 .

[24]  Samuel K Sia,et al.  Assembly of complex cell microenvironments using geometrically docked hydrogel shapes , 2013, Proceedings of the National Academy of Sciences.

[25]  Nobuyuki Magome,et al.  Electrospun nanofibers as a tool for architecture control in engineered cardiac tissue. , 2011, Biomaterials.

[26]  A D McCulloch,et al.  Microstructural model of perimysial collagen fibers for resting myocardial mechanics during ventricular filling. , 1997, The American journal of physiology.

[27]  W. Shim,et al.  Identification and Characterization of Calcium Sparks in Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells , 2012, PloS one.

[28]  J. Bechhoefer,et al.  Erratum: ‘‘Calibration of atomic‐force microscope tips’’ [Rev. Sci. Instrum. 64, 1868 (1993)] , 1993 .

[29]  Sean P Sheehy,et al.  Myocyte shape regulates lateral registry of sarcomeres and contractility. , 2012, The American journal of pathology.

[30]  Koichiro Uto,et al.  Substrate stiffness modulates gene expression and phenotype in neonatal cardiomyocytes in vitro. , 2012, Tissue engineering. Part A.

[31]  Thomas Rau,et al.  Human Engineered Heart Tissue as a Versatile Tool in Basic Research and Preclinical Toxicology , 2011, PloS one.

[32]  Megan L. McCain,et al.  Ensembles of engineered cardiac tissues for physiological and pharmacological study: heart on a chip. , 2011, Lab on a chip.

[33]  Meifeng Xu,et al.  Laser-patterned stem-cell bridges in a cardiac muscle model for on-chip electrical conductivity analyses. , 2012, Lab on a chip.

[34]  A. Gerdes,et al.  Structural remodeling and mechanical dysfunction of cardiac myocytes in heart failure. , 1995, Journal of molecular and cellular cardiology.

[35]  Sean P. Palecek,et al.  Robust cardiomyocyte differentiation from human pluripotent stem cells via temporal modulation of canonical Wnt signaling , 2012, Proceedings of the National Academy of Sciences.

[36]  Wei-Zhong Zhu,et al.  Structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells. , 2013, Stem cells and development.

[37]  Nenad Bursac,et al.  Tissue-engineered cardiac patch for advanced functional maturation of human ESC-derived cardiomyocytes. , 2013, Biomaterials.

[38]  Ali Khademhosseini,et al.  Microwell-mediated control of embryoid body size regulates embryonic stem cell fate via differential expression of WNT5a and WNT11 , 2009, Proceedings of the National Academy of Sciences.

[39]  Kumaraswamy Nanthakumar,et al.  Biowire: a New Platform for Maturation of Human Pluripotent Stem Cell Derived Cardiomyocytes Pubmed Central Canada , 2022 .