Pluripotent Human Stem Cells

Phillips, Blaine; Crook, Jeremy Micah

doi:10.2165/11532270-000000000-00000

Cited by 22 publications

(8 citation statements)

References 102 publications

(90 reference statements)

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“…These new reprogramming technologies would enable not only the generation of pluripotent cells for autologous cell therapies, but would also allow for the application of human iPS cells to specific issues in drug research and in safety pharmacology or toxicology studies (reviewed in Ebert and Svendsen 2010; Phillips and Crook 2010; Rowntree and McNeish 2010), as well as for the analysis of pathomechanisms of heritable diseases with “disease-specific” iPS cells (e.g. Dimos et al 2008; Park et al 2008; Ebert et al 2009; reviewed in Saha and Jaenisch 2009; Lee and Studer 2010).…”

Section: Characteristics Of In Vitro–cultured Pluripotent Stem Cellsmentioning

confidence: 99%

Present state and future perspectives of using pluripotent stem cells in toxicology research

2011

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The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed.

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Section: Characteristics Of In Vitro–cultured Pluripotent Stem Cellsmentioning

confidence: 99%

Present state and future perspectives of using pluripotent stem cells in toxicology research

2011

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“…The potential of ESCs to differentiate into almost all cell types not only provides an unlimited number of cells but also has attracted great interest in medical applications such as pharmaceutical 31 and cell therapy. 32 For example, pluripotent stem cells derived from ESCs can be used in drug development, drug screening, and cell toxicology.…”

Section: Embryonic Stem Cellsmentioning

confidence: 99%

Stem cells in microfluidics

Lin²,

Lee³

2011

Biomicrofluidics

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Microfluidic techniques have been recently developed for cell-based assays. In microfluidic systems, the objective is for these microenvironments to mimic in vivo surroundings. With advantageous characteristics such as optical transparency and the capability for automating protocols, different types of cells can be cultured, screened, and monitored in real time to systematically investigate their morphology and functions under well-controlled microenvironments in response to various stimuli. Recently, the study of stem cells using microfluidic platforms has attracted considerable interest. Even though stem cells have been studied extensively using bench-top systems, an understanding of their behavior in in vivo-like microenvironments which stimulate cell proliferation and differentiation is still lacking. In this paper, recent cell studies using microfluidic systems are first introduced. The various miniature systems for cell culture, sorting and isolation, and stimulation are then systematically reviewed. The main focus of this review is on papers published in recent years studying stem cells by using microfluidic technology. This review aims to provide experts in microfluidics an overview of various microfluidic systems for stem cell research.

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“…Many studies have been carried out to identify the most advantageous strategies to drive the differentiation towards the desired cell phenotypes thus allowing valuable investigations in basic research and suggesting useful perspectives for regenerative purposes. In the cardiovascular field, hESCs provide a powerful tool to clarify key developmental steps of cardiac embryogenesis [2], to develop reliable in vitro models for drug toxicity screening [3] and are considered a promising source for cell-based therapies in pathologies such as myocardial infarction or pace-maker center dysfunction [4]. Studies involving hESCs differentiated toward the cardiac phenotype are rather demanding due to difficulties such as i) low efficiency process of differentiation [5]; ii) dishomogeneity of cell phenotypes; iii) laborious phenotypic characterization, e.g.…”

Section: Introductionmentioning

confidence: 99%

Mathematical modelling of the action potential of human embryonic stem cell derived cardiomyocytes

et al. 2012

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BackgroundHuman embryonic stem cell derived cardiomyocytes (hESC-CMs) hold high potential for basic and applied cardiovascular research. The development of a reliable simulation platform able to mimic the functional properties of hESC-CMs would be of considerable value to perform preliminary test complementing in vitro experimentations.MethodsWe developed the first computational model of hESC-CM action potential by integrating our original electrophysiological recordings of transient-outward, funny, and sodium-calcium exchanger currents and data derived from literature on sodium, calcium and potassium currents in hESC-CMs.ResultsThe model is able to reproduce basal electrophysiological properties of hESC-CMs at 15 40 days of differentiation (Early stage). Moreover, the model reproduces the modifications occurring through the transition from Early to Late developmental stage (50-110, days of differentiation). After simulated blockade of ionic channels and pumps of the sarcoplasmic reticulum, Ca2+ transient amplitude was decreased by 12% and 33% in Early and Late stage, respectively, suggesting a growing contribution of a functional reticulum during maturation. Finally, as a proof of concept, we tested the effects induced by prototypical channel blockers, namely E4031 and nickel, and their qualitative reproduction by the model.ConclusionsThis study provides a novel modelling tool that may serve useful to investigate physiological properties of hESC-CMs.

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Pluripotent Human Stem Cells

Cited by 22 publications

References 102 publications

Present state and future perspectives of using pluripotent stem cells in toxicology research

Present state and future perspectives of using pluripotent stem cells in toxicology research

Stem cells in microfluidics

Mathematical modelling of the action potential of human embryonic stem cell derived cardiomyocytes

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