scholarly journals Simultaneous Measurement of Contractile Force and Field Potential of Dynamically Beating Human iPS Cell-Derived Cardiac Cell Sheet-Tissue with Flexible Electronics

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Takashi Ohya ◽  
Haruki Ohtomo ◽  
Tetsutaro Kikuchi ◽  
Daisuke Sasaki ◽  
Yohei Kawamura ◽  
...  
Keyword(s):  
Functional Assessment ◽  
Flexible Electronics ◽  
Cell Sheet ◽  
Field Potential ◽  
Contractile Force ◽  
Cardiac Cell ◽  
Ips Cell ◽  
Cardiac Tissues ◽  
Induced Pluripotent

Human induced pluripotent stem (iPS) cell-derived cardiomyocytes are used for in vitro pharmacological and pathological studies worldwide. In particular, the functional assessment of cardiac tissues created from iPS cell-derived cardiomyocytes...

scholarly journals Contractile force measurement of human induced pluripotent stem cell-derived cardiac cell sheet-tissue

PLoS ONE ◽  
2018 ◽  
Vol 13 (5) ◽  
pp. e0198026 ◽  
Author(s):  
Daisuke Sasaki ◽  
Katsuhisa Matsuura ◽  
Hiroyoshi Seta ◽  
Yuji Haraguchi ◽  
Teruo Okano ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Force Measurement ◽  
Cell Sheet ◽  
Induced Pluripotent Stem Cell ◽  
Contractile Force ◽  
Cardiac Cell ◽  
Induced Pluripotent

Abstract 30: In vitro Fabrication of Human Cardiac Tissues With Porcine Perfusable Blood Vessels

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Akitoshi Inui ◽  
Hidekazu Sekine ◽  
Kazunori Sano ◽  
Izumi Dobashi ◽  
Azumi Yoshida ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Cardiac Tissue ◽  
Severe Heart Failure ◽  
Perfusion Culture ◽  
Cardiac Cell ◽  
Cell Sheets ◽  
Cardiac Tissues ◽  
Bioreactor System ◽  
Human Cardiac Tissue

The definitive treatment of severe heart failure is heart transplantation; however the number of heart transplantation procedures performed in Japan per year ranges from 30-40 due to donor shortage. Therefore, recently other treatments such as ventricular assist device or regenerative therapy by human cardiac tissue engineering have been developed and are considered as appropriate alternatives. We have developed an original technology, which was named cell-sheet based tissue engineering to fabricate functional three-dimensional tissue by layering cell sheets. The utilization of this technique allowed us to successfully engineer thick rat cardiac tissue with perfusable blood vessels in vitro. Here, we demonstrate a technique to engineer human cardiac tissue with perfusable blood vessels using cardiac cell sheets derived from human induced pluripotent stem cells, and porcine small intestine as a vascular bed for perfusion culture. The small intestine was harvested from with a branch of the superior mesenteric artery and vein and underwent mucosal resection after harvested tissue was cut open. To engineer cardiac tissue with perfusable blood vessels, cardiac cell sheets co-cultured with endothelial cells, were triple-layered and then was overlaid on the vascular bed in the bioreactor system. One day after perfusion culture, overlaid cardiac tissues pulsated spontaneously and were synchronized. The cardiac tissue construct was viable tissue without any observable necrosis. Furthermore we examined the possibility of transplantation of the in vitro engineered human cardiac tissue with the connectable host artery and vein. Engineered cardiac tissue was removed from the bioreactor system after 4-day perfusion, and transplanted to another pig heart. The branch of the superior mesenteric artery and vein of the graft were then reconnected to the host internal thoracic artery and vein. When the cardiac tissue reperfused, it began to beat spontaneously after a few minutes. We believe that this method is useful to fabricate functional cardiac tissue and may become an appropriate treatment for severe heart failure.

scholarly journals Phenotypic Screening with Human iPS Cell–Derived Cardiomyocytes

2013 ◽  
Vol 18 (10) ◽  
pp. 1203-1211 ◽  
Author(s):  
Coby Carlson ◽  
Chad Koonce ◽  
Natsuyo Aoyama ◽  
Shannon Einhorn ◽  
Steve Fiene ◽  
...  
Keyword(s):  
Drug Discovery ◽  
High Throughput Screening ◽  
Phenotypic Screening ◽  
Ips Cell ◽  
Hypertrophic Response ◽  
Cardiac Condition ◽  
Vitro Model ◽  
Induced Pluripotent ◽  
The Many

A major hurdle for cardiovascular disease researchers has been the lack of robust and physiologically relevant cell-based assays for drug discovery. Derivation of cardiomyocytes from human-induced pluripotent stem (iPS) cells at high purity, quality, and quantity enables the development of relevant models of human cardiac disease with source material that meets the demands of high-throughput screening (HTS). Here we demonstrate the utility of iPS cell–derived cardiomyocytes as an in vitro model of cardiac hypertrophy. Exposure of cardiomyocytes to endothelin 1 (ET-1) leads to reactivation of fetal genes, increased cell size, and robust expression of B-type natriuretic peptide (BNP). Using this system, we developed a suite of assays focused on BNP detection, most notably a high-content imaging-based assay designed for phenotypic screening. Miniaturization of this assay to a 384-well format enabled the profiling of a small set of tool compounds known to modulate the hypertrophic response. The assays described here provide consistent and reliable results and have the potential to increase our understanding of the many mechanisms underlying this complex cardiac condition. Moreover, the HTS-compatible workflow allows for the incorporation of human biology into early phases of drug discovery and development.

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.

Induced human pluripotent stem cells: promises and open questions

2009 ◽  
Vol 390 (9) ◽  
Author(s):  
Alexandra Rolletschek ◽  
Anna M. Wobus
Keyword(s):  
Pluripotent Stem Cells ◽  
Viral Vectors ◽  
Insertional Mutagenesis ◽  
Ips Cells ◽  
Patient Specific ◽  
Ips Cell ◽  
Open Questions ◽  
Induced Pluripotent ◽  
Selective Differentiation

Abstract Adult cells have been reprogrammed into induced pluripotent stem (iPS) cells by introducing pluripotency-associated transcription factors. Here, we discuss recent advances and challenges of in vitro reprogramming and future prospects of iPS cells for their use in diagnosis and cell therapy. The generation of patient-specific iPS cells for clinical application requires alternative strategies, because genome-integrating viral vectors may cause insertional mutagenesis. Moreover, when suitable iPS cell lines will be available, efficient and selective differentiation protocols are needed to generate transplantable grafts. Finally, we point to the requirement of a regulatory framework necessary for the commercial use of iPS cells.

scholarly journals Human Erbb2-induced Erk Activity Robustly Stimulates Cycling and Functional Remodeling of Rat and Human Cardiomyocytes

2020 ◽  
Author(s):  
Nicholas Strash ◽  
Sophia DeLuca ◽  
Geovanni Janer Carattini ◽  
Soon Chul Heo ◽  
Ryne Gorsuch ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Induced Pluripotent Stem Cell ◽  
Neonatal Rat ◽  
Mutant Form ◽  
Cardiac Tissues ◽  
Human Cardiomyocytes ◽  
Heart Repair ◽  
Induced Pluripotent ◽  
Species Specific

Multiple mitogenic pathways capable of promoting mammalian cardiomyocyte (CM) proliferation have been identified as potential candidates for functional heart repair following myocardial infarction. However, it is unclear whether the effects of these mitogens are species-specific and how they directly compare in the same cardiac setting. Here, we examined how CM-specific lentiviral expression of various candidate mitogens affects human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and neonatal rat ventricular myocytes (NRVMs) in vitro. In 2D-cultured CMs from both species, and in highly mature 3D-engineered cardiac tissues generated from NRVMs, a constitutively-active mutant form of the human gene Erbb2 (cahErbb2) was the most potent tested mitogen. Persistent expression of cahErbb2 induced CM proliferation, sarcomere loss, and remodeling of tissue structure and function, which were attenuated by small molecule inhibitors of Erk signaling. These results suggest transient activation of Erbb2/Erk axis in cardiomyocytes as a potential strategy for regenerative heart repair.

scholarly journals Current strategies of mechanical stimulation for maturation of cardiac microtissues

2021 ◽  
Author(s):  
Maria Carlos-Oliveira ◽  
Ferran Lozano-Juan ◽  
Paola Occhetta ◽  
Roberta Visone ◽  
Marco Rasponi
Keyword(s):  
Mechanical Stimulation ◽  
Pluripotent Stem Cells ◽  
Positive Response ◽  
Cyclic Strain ◽  
Disease Modelling ◽  
Mechanical Forces ◽  
Cardiac Tissues ◽  
Cell Sources ◽  
Induced Pluripotent

AbstractThe most advanced in vitro cardiac models are today based on the use of induced pluripotent stem cells (iPSCs); however, the maturation of cardiomyocytes (CMs) has not yet been fully achieved. Therefore, there is a rising need to move towards models capable of promoting an adult-like cardiomyocytes phenotype. Many strategies have been applied such as co-culture of cardiomyocytes, with fibroblasts and endothelial cells, or conditioning them through biochemical factors and physical stimulations. Here, we focus on mechanical stimulation as it aims to mimic the different mechanical forces that heart receives during its development and the post-natal period. We describe the current strategies and the mechanical properties necessary to promote a positive response in cardiac tissues from different cell sources, distinguishing between passive stimulation, which includes stiffness, topography and static stress and active stimulation, encompassing cyclic strain, compression or perfusion. We also highlight how mechanical stimulation is applied in disease modelling.

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