Human induced pluripotent stem cell-derived beating cardiac tissues on paper

Lab on a Chip ◽  
2015 ◽  
Vol 15 (22) ◽  
pp. 4283-4290 ◽  
Author(s):  
Li Wang ◽  
Cong Xu ◽  
Yujuan Zhu ◽  
Yue Yu ◽  
Ning Sun ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Beating Heart ◽  
Cardiac Tissues ◽  
Human Ipscs ◽  
Induced Pluripotent

We demonstrate the first attempt to differentiate human-iPSCs into cardiac microtissues on paper and create “a beating heart on paper.”

Abstract 161: Induced Pluripotent Stem Cell-based Model of Cardiac Arrhythmia: New Platform for Drug Screen

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
LouJin Song ◽  
Masayuki Yazawa
Keyword(s):  
Stem Cell ◽  
Action Potentials ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Calcium Handling ◽  
Drug Screen ◽  
Cardiac Diseases ◽  
Timothy Syndrome ◽  
Human Ipscs ◽  
Induced Pluripotent

Human induced pluripotent stem cell (iPSC)-based model of cardiac diseases has been proved to be useful and valuable for identifying new therapeutics. However, the use of human iPSC-based model of cardiac diseases for drug screen is hampered by the high-cost and complexity of methods used for reprogramming, in vitro differentiation, and phenotyping. To address the limitations, we first optimized a protocol for reprogramming of human fibroblasts and keratinocytes into pluripotency using single lipofection and the episomal vectors in a 24-well plate format. This method allowed us to generate multiple lines of integration-free and feeder-free iPSCs from seven patients with cardiac diseases and three controls. Second, we differentiated human iPSCs derived from Timothy syndrome patients into cardiomyocytes using a monolayer differentiation method. We found that Timothy syndrome cardiomyocytes showed slower, irregular contractions and abnormal calcium handling compared to controls, which were consistent with previous reports using a retroviral method for reprogramming and using an embryoid body-based method for cardiac differentiation. Third, we developed an efficient approach for recording action potentials and calcium transients simultaneously in control and patient cardiomyocytes using genetically encoded fluorescent indicators, ArcLight and R-GECO1. The dual optical recordings enabled us to observe prolonged action potentials and abnormal calcium handling in Timothy syndrome cardiomyocytes. We confirmed that roscovitine rescued the phenotypes in Timothy syndrome cardiomyocytes and these findings were consistent with previous studies using conventional electrophysiological recordings and calcium imaging with dyes. The approaches using our optimized methods and dual optical recordings will improve iPSC applicability for disease modeling to test potential therapeutics. With those new approaches in hand, next we plan to use the iPSC-based model of Timothy syndrome to investigate novel molecules involved in the pathogenesis of Timothy syndrome and to screen and identify new therapeutic compounds for Timothy syndrome patients.

Human induced pluripotent stem cell-derived cardiac tissue on a thin collagen membrane with natural microstructures

2016 ◽  
Vol 4 (11) ◽  
pp. 1655-1662 ◽  
Author(s):  
Li Wang ◽  
Xiaoqing Zhang ◽  
Cong Xu ◽  
Hui Liu ◽  
Jianhua Qin
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Cardiac Tissue ◽  
Induced Pluripotent Stem Cell ◽  
Collagen Membrane ◽  
Cardiac Tissues ◽  
New Strategy ◽  
Induced Pluripotent

We present a new strategy to produce a thin collagen membrane from porcine tendons and engineered cardiac tissues using hiPSC-derived cardiomyocytes.

scholarly journals Human Induced Pluripotent Stem-Cell-Derived Cardiomyocytes as Models for Genetic Cardiomyopathies

2019 ◽  
Vol 20 (18) ◽  
pp. 4381 ◽  
Author(s):  
Andreas Brodehl ◽  
Hans Ebbinghaus ◽  
Marcus-André Deutsch ◽  
Jan Gummert ◽  
Anna Gärtner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Patient Specific ◽  
Promising Alternative ◽  
Human Ipscs ◽  
Genetic Landscape ◽  
Inherited Cardiomyopathies ◽  
Induced Pluripotent ◽  
Human Ipsc

In the last few decades, many pathogenic or likely pathogenic genetic mutations in over hundred different genes have been described for non-ischemic, genetic cardiomyopathies. However, the functional knowledge about most of these mutations is still limited because the generation of adequate animal models is time-consuming and challenging. Therefore, human induced pluripotent stem cells (iPSCs) carrying specific cardiomyopathy-associated mutations are a promising alternative. Since the original discovery that pluripotency can be artificially induced by the expression of different transcription factors, various patient-specific-induced pluripotent stem cell lines have been generated to model non-ischemic, genetic cardiomyopathies in vitro. In this review, we describe the genetic landscape of non-ischemic, genetic cardiomyopathies and give an overview about different human iPSC lines, which have been developed for the disease modeling of inherited cardiomyopathies. We summarize different methods and protocols for the general differentiation of human iPSCs into cardiomyocytes. In addition, we describe methods and technologies to investigate functionally human iPSC-derived cardiomyocytes. Furthermore, we summarize novel genome editing approaches for the genetic manipulation of human iPSCs. This review provides an overview about the genetic landscape of inherited cardiomyopathies with a focus on iPSC technology, which might be of interest for clinicians and basic scientists interested in genetic cardiomyopathies.

scholarly journals Chronic optical pacing conditioning of h-iPSC engineered cardiac tissues

2019 ◽  
Vol 10 ◽  
pp. 204173141984174 ◽  
Author(s):  
Marc Dwenger ◽  
William J Kowalski ◽  
Fei Ye ◽  
Fangping Yuan ◽  
Joseph P Tinney ◽  
...  
Keyword(s):  
Stem Cell ◽  
Electrical Stimulation ◽  
Pluripotent Stem Cell ◽  
Cardiac Tissue ◽  
Induced Pluripotent Stem Cell ◽  
Mechanical Stretch ◽  
In Vitro Models ◽  
Cardiac Tissues ◽  
Induced Pluripotent

The immaturity of human induced pluripotent stem cell derived engineered cardiac tissues limits their ability to regenerate damaged myocardium and to serve as robust in vitro models for human disease and drug toxicity studies. Several chronic biomimetic conditioning protocols, including mechanical stretch, perfusion, and/or electrical stimulation promote engineered cardiac tissue maturation but have significant technical limitations. Non-contacting chronic optical stimulation using heterologously expressed channelrhodopsin light-gated ion channels, termed optogenetics, may be an advantageous alternative to chronic invasive electrical stimulation for engineered cardiac tissue conditioning. We designed proof-of-principle experiments to successfully transfect human induced pluripotent stem cell derived engineered cardiac tissues with a desensitization resistant, chimeric channelrhodopsin protein, and then optically paced engineered cardiac tissues to accelerate maturation. We transfected human induced pluripotent stem cell engineered cardiac tissues using an adeno-associated virus packaged chimeric channelrhodopsin and then verified optically paced by whole cell patch clamp. Engineered cardiac tissues were then chronically optically paced above their intrinsic beat rates in vitro from day 7 to 14. Chronically optically paced resulted in improved engineered cardiac tissue electrophysiological properties and subtle changes in the expression of some cardiac relevant genes, though active force generation and histology were unchanged. These results validate the feasibility of a novel chronically optically paced paradigm to explore non-invasive and scalable optically paced–induced engineered cardiac tissue maturation strategies.

scholarly journals Therapeutic potential of clinical-grade human induced pluripotent stem cell-derived cardiac tissues

JTCVS Open ◽  
2021 ◽  
Author(s):  
Hiroaki Osada ◽  
Masahide Kawatou ◽  
Daiki Fujita ◽  
Yasuhiko Tabata ◽  
Kenji Minatoya ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Therapeutic Potential ◽  
Induced Pluripotent Stem Cell ◽  
Clinical Grade ◽  
Cardiac Tissues ◽  
Induced Pluripotent

Chronic Optogenetic Pacing of Human-Induced Pluripotent Stem Cell-Derived Engineered Cardiac Tissues

2020 ◽  
pp. 151-169
Author(s):  
Marc Dwenger ◽  
William J. Kowalski ◽  
Hidetoshi Masumoto ◽  
Takeichiro Nakane ◽  
Bradley B. Keller
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Cardiac Tissues ◽  
Induced Pluripotent
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