scholarly journals Patient-Specific Induced Pluripotent Stem Cell Cardiac Myocytes as Predictors of Sudep Risk

2016 ◽  
Vol 110 (3) ◽  
pp. 111a
Author(s):  
Chad R. Frasier ◽  
Helen Zhang ◽  
James Offord ◽  
David S. Auerbach ◽  
Jack M. Paren ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cardiac Myocytes ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Patient Specific ◽  
Induced Pluripotent

scholarly journals Elucidating arrhythmogenic mechanisms of long-QT syndrome CALM1-F142L mutation in patient-specific induced pluripotent stem cell-derived cardiomyocytes

2017 ◽  
Vol 113 (5) ◽  
pp. 531-541 ◽  
Author(s):  
Marcella Rocchetti ◽  
Luca Sala ◽  
Lisa Dreizehnter ◽  
Lia Crotti ◽  
Daniel Sinnecker ◽  
...  
Keyword(s):  
Stem Cell ◽  
Long Qt Syndrome ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Patient Specific ◽  
Long Qt ◽  
Qt Syndrome ◽  
Induced Pluripotent

scholarly journals Patient-Specific Induced Pluripotent Stem-Cell Models for Long-QT Syndrome

2010 ◽  
Vol 363 (15) ◽  
pp. 1397-1409 ◽  
Author(s):  
Alessandra Moretti ◽  
Milena Bellin ◽  
Andrea Welling ◽  
Christian Billy Jung ◽  
Jason T. Lam ◽  
...  
Keyword(s):  
Stem Cell ◽  
Long Qt Syndrome ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Patient Specific ◽  
Cell Models ◽  
Long Qt ◽  
Qt Syndrome ◽  
Induced Pluripotent ◽  
Stem Cell Models

scholarly journals Machine Learning Approach to Automated Quality Identification of Human Induced Pluripotent Stem Cell Colony Images

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Henry Joutsijoki ◽  
Markus Haponen ◽  
Jyrki Rasku ◽  
Katriina Aalto-Setälä ◽  
Martti Juhola
Keyword(s):  
Machine Learning ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Patient Specific ◽  
Support Vector ◽  
Ips Cell ◽  
Cell Technology ◽  
Induced Pluripotent

The focus of this research is on automated identification of the quality of human induced pluripotent stem cell (iPSC) colony images. iPS cell technology is a contemporary method by which the patient’s cells are reprogrammed back to stem cells and are differentiated to any cell type wanted. iPS cell technology will be used in future to patient specific drug screening, disease modeling, and tissue repairing, for instance. However, there are technical challenges before iPS cell technology can be used in practice and one of them is quality control of growing iPSC colonies which is currently done manually but is unfeasible solution in large-scale cultures. The monitoring problem returns to image analysis and classification problem. In this paper, we tackle this problem using machine learning methods such as multiclass Support Vector Machines and several baseline methods together with Scaled Invariant Feature Transformation based features. We perform over 80 test arrangements and do a thorough parameter value search. The best accuracy (62.4%) for classification was obtained by using ak-NN classifier showing improved accuracy compared to earlier studies.

Abstract 142: Modeling Drug-Induced Long QT Syndrome with Patient-Specific Induced Pluripotent Stem Cell-Derived Cardiomyocytes

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Francesca Stillitano ◽  
Ioannis Karakikes ◽  
Chi-wai Kong ◽  
Brett Martinelli ◽  
Ronald Li ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Patient Specific ◽  
Dependent Manner ◽  
Long Qt ◽  
Drug Induced ◽  
Qt Syndrome ◽  
Induced Pluripotent ◽  
Dose Dependent

Long QT syndrome (LQTS) is characterized by prolonged cardiac repolarization time and increased risk of ventricular arrhythmia. LQTS can be either inherited or induced notably after drugs intake. Mutations in genes encoding cardiac ion channels have been reported to underlie inherited LQTS. In contrast, drug-induced LQTS (diLQTS) most frequently arises from altered function of the hERG channel; the risk of developing diLQTS varies largely between subjects and most people who have life-threatening diLQTS have no known genetic risk factors. We investigated whether the susceptibility to develop diLQTS observed in vivo can be recapitulated in vitro using patient-specific induced pluripotent stem cell (iPSC) technology. We collected skin fibroblasts from ten subjects who developed significant diLQTS after administration of Sotalol and/or Erythromycin. Ten other individuals who displayed no changes in QT interval after administration of the same drugs, were selected. iPSC were generated by retroviral delivery of Oct4, Sox2, Nanog and Klf4 in 17 of the 20 individuals. We report preliminary results obtained from iPSC-derived cardiomyocytes (iPSC-CMs) of two subjects. All experiments were performed in a blinded fashion without knowledge of the associated clinical phenotype. Cardiac differentiation of iPSC resulted in the generation of spontaneously beating embryoid bodies. iPSC-CMs showed positive staining for TNNT2, ACTN2 and Cx43. Gene expression analysis confirmed the expression of NKX2.5, MLC2v, MYH6 and MYH7, and of the relevant KCNH2 gene. The two lines had similar basal electrophysiological properties as assessed by measurements of action potential (AP) by patch-clamp technique and extracellular field potentials (FP) using micro-electrode array (MEA). E4031, a classical HERG blocker, significantly prolonged the FP duration (FPD) in a dose-dependent manner in both lines (EC50: 30.19 and 51.57 respectively). When both Sotalol and Erythromicin were used, FPD was prolonged in one of the two samples in a dose-dependent manner (EC50Sotalol: 100; EC50Erythr: 9.64) while drug response was blunted in the other cell line. This study suggests that patient-specific iPSC can be used to model the functional abnormalities observed in acquired diLQTS.

scholarly journals N-cadherin overexpression enhances the reparative potency of human-induced pluripotent stem cell-derived cardiac myocytes in infarcted mouse hearts

2019 ◽  
Vol 116 (3) ◽  
pp. 671-685 ◽  
Author(s):  
Xi Lou ◽  
Meng Zhao ◽  
Chengming Fan ◽  
Vladimir G Fast ◽  
Mani T Valarmathi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Infarct Size ◽  
Cardiac Myocytes ◽  
Pluripotent Stem Cell ◽  
Myogenic Differentiation ◽  
Functional Integration ◽  
Induced Pluripotent Stem Cell ◽  
Left Ventricular ◽  
Cardiac Functions ◽  
Induced Pluripotent

Abstract Aims In regenerative medicine, cellular cardiomyoplasty is one of the promising options for treating myocardial infarction (MI); however, the efficacy of such treatment has shown to be limited due to poor survival and/or functional integration of implanted cells. Within the heart, the adhesion between cardiac myocytes (CMs) is mediated by N-cadherin (CDH2) and is critical for the heart to function as an electromechanical syncytium. In this study, we have investigated whether the reparative potency of human-induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) can be enhanced through CDH2 overexpression. Methods and results CDH2-hiPSC-CMs and control wild-type (WT)-hiPSC-CMs were cultured in myogenic differentiation medium for 28 days. Using a mouse MI model, the cell survival/engraftment rate, infarct size, and cardiac functions were evaluated post-MI, at Day 7 or Day 28. In vitro, conduction velocities were significantly greater in CDH2-hiPSC-CMs than in WT-hiPSC-CMs. While, in vivo, measurements of cardiac functions: left ventricular (LV) ejection fraction, reduction in infarct size, and the cell engraftment rate were significantly higher in CDH2-hiPSC-CMs treated MI group than in WT-hiPSC-CMs treated MI group. Mechanistically, paracrine activation of ERK signal transduction pathway by CDH2-hiPSC-CMs, significantly induced neo-vasculogenesis, resulting in a higher survival of implanted cells. Conclusion Collectively, these data suggest that CDH2 overexpression enhances not only the survival/engraftment of cultured CDH2-hiPSC-CMs, but also the functional integration of these cells, consequently, the augmentation of the reparative properties of implanted CDH2-hiPSC-CMs in the failing hearts.

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