Human induced pluripotent stem cells and their use in drug discovery for toxicity testing

Scott, Clay W.; Peters, Matthew F.; Dragan, Yvonne P.

doi:10.1016/j.toxlet.2013.02.020

Cited by 139 publications

(123 citation statements)

References 76 publications

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“…Currently, they play a key role in therapeutic and other biotechnological applications such as drug discovery, toxicology, disease modeling, and gene therapy [28]. It is demonstrated that iPSCs are currently being used for high-throughput screening and chronic toxicity assessment of cardiac, hepatic, and nervous tissues [29]. Recent report by Deshmukh et al [30] describes that ES cells and iPSCs are efficiently used to screen cardiac and neurotoxic agents.…”

Section: Tripathy and Mohantymentioning

confidence: 99%

Mesenchymal Stem Cells: An Innovative Approach in Pharmacokinetics

Tripathy¹,

Mohanty²

2017

Asian J Pharm Clin Res

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Multipotent mesenchymal stem cells (MSCs) are special kind of stem cells which originate from mesenchyme. These cells can be used as an imperative tool to study reproductive toxicity, carcinogenicity, mutagenicity, genotoxicity, and pharmacokinetics. This novel system may reveal toxicantinduced etiology, decipher detailed understanding on molecular mechanisms of toxicants induced pathways and also enumerate the safe dose of an investigational product. Hence, this could ultimately replace, improve or overtake current predictive models in toxicology. The particular review describes the utilization of MSCs in different field of toxicological and pharmacological research.

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Section: Tripathy and Mohantymentioning

confidence: 99%

Mesenchymal Stem Cells: An Innovative Approach in Pharmacokinetics

Tripathy¹,

Mohanty²

2017

Asian J Pharm Clin Res

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“…Toxicity tests on cell lines can be evaluated by testing the drug on a variety of cell types for which cell lines are available. These toxicity tests on cell lines can be an indication for the drug treatments for the cancer type which was studied 14,15 .…”

Section: In Vitro Systems For Toxicity Testingmentioning

confidence: 99%

“…Normal cells from humaninduced pluripotent stem cells (hiPSC) and improved epithelial cell culture conditions can be used nowadays to broaden in vitro toxicity testing at the normal cellular level 14,15 . hiPSC-derived cardiomyocytes, endothelial cells, hepatocytes, and neuronal cells are commercially available.…”

Section: In Vitro Systems For Toxicity Testingmentioning

confidence: 99%

Applications of cell culture studies in pharmaceutical technology

Şahin¹,

Mesut²,

Özsoy³

2017

actapharm

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“…Suffice to say, an iPSC-based approach for screening incorporates disease, cellular, and patient specificity into highthroughput screening in a manner previously not possible [28,29]. Control, disease-specific, and engineered iPSCs and their secondary derivatives could be used in numerous Tumor line; lack patient and disease specificity; therefore, difficult to determine biological significance; difficult to maintain characteristics in culture Rodent cells Abundant supply; difficult to obtain functional data of neurological functions; models may lack human-specific response Zebrafish Abundant supply; lack patient and disease specificity; difficult to culture cells, immature cells; wider species differences and differing biological response types of screens, including large-scale small molecules, mechanism of action, repurposing of FDA-approved drugs, toxicity-related, high-content, and genomic types [30,31]. Each of these screens utilizes distinct screening agents, including siRNAs, natural compounds, biologics, small molecules, and even FDA-approved drug libraries [27].…”

Section: Modeling Disease Using Human Cells In General and Psc-derivementioning

confidence: 99%

Induced Pluripotent Stem Cell Models to Enable In Vitro Models for Screening in the Central Nervous System

Hunsberger

Efthymiou

Malik

et al. 2015

Stem Cells and Development

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There is great need to develop more predictive drug discovery tools to identify new therapies to treat diseases of the central nervous system (CNS). Current nonpluripotent stem cell-based models often utilize non-CNS immortalized cell lines and do not enable the development of personalized models of disease. In this review, we discuss why in vitro models are necessary for translational research and outline the unique advantages of induced pluripotent stem cell (iPSC)-based models over those of current systems. We suggest that iPSC-based models can be patient specific and isogenic lines can be differentiated into many neural cell types for detailed comparisons. iPSC-derived cells can be combined to form small organoids, or large panels of lines can be developed that enable new forms of analysis. iPSC and embryonic stem cell-derived cells can be readily engineered to develop reporters for lineage studies or mechanism of action experiments further extending the utility of iPSC-based systems. We conclude by describing novel technologies that include strategies for the development of diversity panels, novel genomic engineering tools, new three-dimensional organoid systems, and modified high-content screens that may bring toxicology into the 21st century. The strategic integration of these technologies with the advantages of iPSC-derived cell technology, we believe, will be a paradigm shift for toxicology and drug discovery efforts.Disease Modeling D iseases of the central nervous system (CNS) affect a large number of people, but therapeutic intervention is hampered by the lack of useful models for many of these diseases. Current research on human subjects, particularly for drug discovery for CNS diseases, is severely (and appropriately) limited by ethical guidelines. Therefore, surrogate models are needed that share important anatomical, physiological, and genetic features to advance new treatments and therapies for CNS diseases [1].Developing rapid and effective therapies for CNS diseases requires the availability of in vitro models that accurately recapitulate disease phenotypes and predict patient treatment response. A proper model must be both sensitive and predictive while reflecting both normal and disease processes. Equally important, these models should enable the investigation of genetic and environmental risk factors contributing to diseases in a rapid and economical way. Currently used models often do not reflect a typical human response [2-4], despite efforts underway to better characterize these models and increase their preclinical value in predicting safety and efficacy in the clinic [5,6]. Therefore, there is a great need to develop disease-and patient-specific models from cells directly affected in CNS disorders. These cellbased models, we envision, could either replace or supplement current animal models and enable the efficient translation of basic research into the clinical setting. Limitations with current CNS modelsCurrently, drug discovery relies on the use of animalbased or cell-based models, ...

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Human induced pluripotent stem cells and their use in drug discovery for toxicity testing

Cited by 139 publications

References 76 publications

Mesenchymal Stem Cells: An Innovative Approach in Pharmacokinetics

Mesenchymal Stem Cells: An Innovative Approach in Pharmacokinetics

Applications of cell culture studies in pharmaceutical technology

Induced Pluripotent Stem Cell Models to Enable In Vitro Models for Screening in the Central Nervous System

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