A Microfluidic Bioreactor for Toxicity Testing of Stem Cell Derived 3D Cardiac Bodies

2016 ◽  
pp. 159-168 ◽  
Author(s):  
Jonas Christoffersson ◽  
Gunnar Bergström ◽  
Kristin Schwanke ◽  
Henning Kempf ◽  
Robert Zweigerdt ◽  
...  
Keyword(s):  
Stem Cell ◽  
Toxicity Testing

Toxicity testing using hematopoietic stem cell assays

2007 ◽  
Vol 2 (6) ◽  
pp. 947-956 ◽  
Author(s):  
E Clarke ◽  
C Pereira ◽  
R Chaney ◽  
S Woodside ◽  
AC Eaves ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Toxicity Testing ◽  
Hematopoietic Stem ◽  
Cell Assays

Microphysiological human stem cell systems for toxicity testing

2018 ◽  
Vol 295 ◽  
pp. S25
Author(s):  
S. Coecke ◽  
G. Bowe ◽  
P. Browne
Keyword(s):  
Stem Cell ◽  
Toxicity Testing ◽  
Human Stem Cell ◽  
Cell Systems

Microfluidic devices for stem-cell cultivation, differentiation and toxicity testing

2017 ◽  
Author(s):  
Holger Becker ◽  
Thomas Hansen-Hagge ◽  
Andreas Kurtz ◽  
Ralf Mrowka ◽  
Stefan Wölfl ◽  
...  
Keyword(s):  
Stem Cell ◽  
Toxicity Testing ◽  
Microfluidic Devices ◽  
Cell Cultivation

scholarly journals Human perinatal stem cell derived extracellular matrix enables rapid maturation of hiPSC-CM structural and functional phenotypes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Travis Block ◽  
Jeffery Creech ◽  
Andre Monteiro da Rocha ◽  
Milos Marinkovic ◽  
Daniela Ponce-Balbuena ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Stem Cell ◽  
Disease Modeling ◽  
Toxicity Testing ◽  
Induced Pluripotent Stem Cell ◽  
Torsades De Pointes ◽  
Mouse Cell ◽  
Human Cardiomyocytes ◽  
Cell Assays

Abstract The immature phenotype of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) is a major limitation to the use of these valuable cells for pre-clinical toxicity testing and for disease modeling. Here we tested the hypothesis that human perinatal stem cell derived extracellular matrix (ECM) promotes hiPSC-CM maturation to a greater extent than mouse cell derived ECM. We refer to the human ECM as Matrix Plus (Matrix Plus) and compare effects to commercially available mouse ECM (Matrigel). hiPSC-CMs cultured on Matrix Plus mature functionally and structurally seven days after thaw from cryopreservation. Mature hiPSC-CMs showed rod-shaped morphology, highly organized sarcomeres, elevated cTnI expression and mitochondrial distribution and function like adult cardiomyocytes. Matrix Plus also promoted mature hiPSC-CM electrophysiological function and monolayers’ response to hERG ion channel specific blocker was Torsades de Pointes (TdP) reentrant arrhythmia activations in 100% of tested monolayers. Importantly, Matrix Plus enabled high throughput cardiotoxicity screening using mature human cardiomyocytes with validation utilizing reference compounds recommended for the evolving Comprehensive In Vitro Proarrhythmia Assay (CiPA) coordinated by the Health and Environmental Sciences Institute (HESI). Matrix Plus offers a solution to the commonly encountered problem of hiPSC-CM immaturity that has hindered implementation of these human based cell assays for pre-clinical drug discovery.

A Paradigm Shift is Required for the Risk Assessment of Potential Human Health After Exposure to Low Level Chemical Exposures

2010 ◽  
Vol 29 (4) ◽  
pp. 344-357 ◽  
Author(s):  
James E. Trosko ◽  
Brad L. Upham
Keyword(s):  
Stem Cell ◽  
Neurological Disorders ◽  
Nuclear Dna ◽  
Cell Communication ◽  
Toxicity Testing ◽  
Adult Stem Cell ◽  
Barker Hypothesis ◽  
Chemical Exposures ◽  
Somatic Diseases ◽  
Potential Human Health

Chemicals are known to be associated with birth defects, cancer, cardiovascular diseases, immunological, reproductive, and neurological disorders. In response to recent reviews of limitations of current concepts and techniques for toxicity testing, this commentary challenges the paradigm that chemicals are directly responsible for DNA damage in the genomic–nuclear DNA in relevant cells of the human body. This challenge is not that mutations do not play roles in human-inherited or somatic diseases but that chemical exposures bring about disease end points by epigenetic mechanisms or by alterations in adult stem cell numbers in utero (ie, the Barker hypothesis) or postnatally, by selecting preexisting mutated cells. Classic concepts, that is, multistage, multimechanism process of carcinogenesis, stem cell theory of cancer, and newer and ignored concepts, such as cancer stem cells and cell−cell communication, will be used to support the view that the toxic effect of chemicals is mediated by nonmutagenic mechanisms at human relevant exposures.

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