Optical-flow based non-invasive analysis of cardiomyocyte contractility

Characterization of cardiomyocyte beat patterns is needed for quality control of cells intended for surgical injection as well as to establish phenotypes in disease modeling or toxicity studies. Optical-flow based analysis of videomicroscopic recordings offer a manipulation-free and efficient characterization of contractile cycles, an important characteristics of cardiomyocyte phenotype. We demonstrate that by appropriate computational analysis of optical flow data one can identify distinct contractile centers and distinguish active cell contractility from passive elastic tissue deformations. Our proposed convergence measure correlates with myosin IIa immuno-localization and is capable to resolve contractile waves and their synchronization within maturing, unlabeled induced pluripotent stem cell-derived cardiomyocyte cultures.

[1]  Michal A. Millrod,et al.  Variability of Action Potentials Within and Among Cardiac Cell Clusters Derived from Human Embryonic Stem Cells , 2016, Scientific Reports.

[2]  Sonja Stoelzle-Feix,et al.  State-of-the-art automated patch clamp: heat activation, action potentials, and high throughput in ion channel screening. , 2014, Methods in molecular biology.

[3]  N. Peppas.  Theoretical Considerations , 2003 .

[4]  K. Node,et al.  Endothelin‐1 Induces Myofibrillar Disarray and Contractile Vector Variability in Hypertrophic Cardiomyopathy–Induced Pluripotent Stem Cell–Derived Cardiomyocytes , 2014, Journal of the American Heart Association.

[5]  S. Taverna,et al.  Rapid and efficient CRISPR/Cas9 gene inactivation in human neurons during human pluripotent stem cell differentiation and direct reprogramming , 2016, Scientific Reports.

[6]  Liang Guo,et al.  Estimating the risk of drug-induced proarrhythmia using human induced pluripotent stem cell-derived cardiomyocytes. , 2011, Toxicological sciences : an official journal of the Society of Toxicology.

[7]  Jerry D. Gibson,et al.  Handbook of Image and Video Processing , 2000 .

[8]  D. Mozaffarian,et al.  Heart disease and stroke statistics--2012 update: a report from the American Heart Association. , 2012, Circulation.

[9]  M. Dembo,et al.  Stresses at the cell-to-substrate interface during locomotion of fibroblasts. , 1999, Biophysical journal.

[10]  C. Verdier,et al.  Traction patterns of tumor cells , 2009, Journal of mathematical biology.

[11]  Joseph C. Wu,et al.  Human Induced Pluripotent Stem Cells as a Platform for Personalized and Precision Cardiovascular Medicine. , 2016, Physiological reviews.

[12]  Shinya Yamanaka,et al.  iPS cells: a game changer for future medicine , 2014, The EMBO journal.

[13]  Gordon Keller,et al.  Induced pluripotent stem cells used to reveal drug actions in a long QT syndrome family with complex genetics , 2013, The Journal of general physiology.

[14]  X. Rabasseda,et al.  A report from the American Heart Association Scientific Sessions 2012 (November 3-7 - Los Angeles, California, USA). , 2013, Drugs of today.

[15]  Joel Stein,et al.  Executive summary: heart disease and stroke statistics--2014 update: a report from the American Heart Association. , 2014, Circulation.

[16]  Nicola Nosengo.  Can you teach old drugs new tricks? , 2016, Nature.

[17]  Gordon Keller,et al.  Production of de novo cardiomyocytes: human pluripotent stem cell differentiation and direct reprogramming. , 2012, Cell stem cell.

[18]  K. Fukuda,et al.  Future prospects for regenerated heart using induced pluripotent stem cells. , 2014, Journal of pharmacological sciences.

[19]  Yasunari Kanda,et al.  Image-based evaluation of contraction-relaxation kinetics of human-induced pluripotent stem cell-derived cardiomyocytes: Correlation and complementarity with extracellular electrophysiology. , 2014, Journal of molecular and cellular cardiology.

[20]  Huei-Sheng Vincent Chen,et al.  Non-cardiomyocytes influence the electrophysiological maturation of human embryonic stem cell-derived cardiomyocytes during differentiation. , 2010, Stem cells and development.

[21]  Nathaniel Huebsch,et al.  Automated Video-Based Analysis of Contractility and Calcium Flux in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Cultured over Different Spatial Scales. , 2015, Tissue engineering. Part C, Methods.

[22]  A. Czirók,et al.  Convective tissue movements play a major role in avian endocardial morphogenesis. , 2012, Developmental biology.

[23]  Ralf Kettenhofen,et al.  State-of-the-Art Automated Patch Clamp Devices: Heat Activation, Action Potentials, and High Throughput in Ion Channel Screening , 2011, Front. Pharmacol..

[24]  Ben Fabry,et al.  Traction fields, moments, and strain energy that cells exert on their surroundings. , 2002, American journal of physiology. Cell physiology.

[25]  I. Karakikes,et al.  Human-induced pluripotent stem cell models of inherited cardiomyopathies , 2014, Current opinion in cardiology.

[26]  András Czirók,et al.  Mesodermal cell displacements during avian gastrulation are due to both individual cell-autonomous and convective tissue movements , 2006, Proceedings of the National Academy of Sciences.

[27]  Jean A Boutin,et al.  High-throughput drug profiling with voltage- and calcium-sensitive fluorescent probes in human iPSC-derived cardiomyocytes. , 2016, American journal of physiology. Heart and circulatory physiology.

[28]  Praveen Shukla,et al.  Chemically defined generation of human cardiomyocytes , 2014, Nature Methods.

[29]  Talicia Tarver,et al.  HEART DISEASE AND STROKE STATISTICS–2014 UPDATE: A REPORT FROM THE AMERICAN HEART ASSOCIATION , 2014 .

[30]  Bruce R. Conklin,et al.  A Non-invasive Platform for Functional Characterization of Stem-Cell-Derived Cardiomyocytes with Applications in Cardiotoxicity Testing , 2015, Stem cell reports.

[31]  J D Humphrey,et al.  Biomechanical experiments on excised myocardium: theoretical considerations. , 1989, Journal of biomechanics.

[32]  Jack Lee,et al.  Multiphysics and multiscale modelling, data–model fusion and integration of organ physiology in the clinic: ventricular cardiac mechanics , 2016, Interface Focus.

[33]  Paul W. Burridge,et al.  Human Stem Cells for Modeling Heart Disease and for Drug Discovery , 2014, Science Translational Medicine.

[34]  B. Bhanu,et al.  Evaluating Cell Processes, Quality, and Biomarkers in Pluripotent Stem Cells Using Video Bioinformatics , 2016, PloS one.

[35]  I. Y. Chen,et al.  Induced pluripotent stem cells: at the heart of cardiovascular precision medicine , 2016, Nature Reviews Cardiology.

[36]  Donald M Bers,et al.  Drug Screening Using a Library of Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes Reveals Disease-Specific Patterns of Cardiotoxicity , 2013, Circulation.

[37]  Katia Bertoldi,et al.  Modeling of cardiac muscle thin films: pre-stretch, passive and active behavior. , 2012, Journal of biomechanics.

[38]  N. Schork.  Personalized medicine: Time for one-person trials , 2015, Nature.

[39]  J. Seidman,et al.  A Tension-Based Model Distinguishes Hypertrophic versus Dilated Cardiomyopathy , 2016, Cell.

[40]  Tomaso Zambelli,et al.  Force-controlled patch clamp of beating cardiac cells. , 2015, Nano letters.

[41]  A. Czirók,et al.  Generation of Functional Cardiomyocytes from Efficiently Generated Human iPSCs and a Novel Method of Measuring Contractility , 2015, PloS one.

[42]  Luke P. Lee,et al.  Human iPSC-based Cardiac Microphysiological System For Drug Screening Applications , 2015, Scientific Reports.

[43]  G. Dreissen,et al.  The constant beat: cardiomyocytes adapt their forces by equal contraction upon environmental stiffening , 2013, Biology Open.

[44]  A. Czirók,et al.  Active cell and ECM movements during development. , 2015, Methods in molecular biology.

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