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Stem Cell Models for Drug Discovery and Toxicology Studies

  1. Wenwei Liu1,
  2. Yaguang Deng1,
  3. Ying Liu1,2,
  4. Wenrong Gong1,
  5. Wenbin Deng1,3,*

Article first published online: 4 JAN 2013

DOI: 10.1002/jbt.21470

Issue

Journal of Biochemical and Molecular Toxicology

Journal of Biochemical and Molecular Toxicology

Special Issue: Special Issue 1: National Institute of Environmental Health Sciences Outstanding New Environmental Scientist Program

Volume 27, Issue 1, pages 17–27, January 2013

Additional Information

How to Cite

Liu, W., Deng, Y., Liu, Y., Gong, W. and Deng, W. (2013), Stem Cell Models for Drug Discovery and Toxicology Studies. J. Biochem. Mol. Toxicol., 27: 17–27. doi: 10.1002/jbt.21470

Author Information

  1. 1

    Medical College, Hubei University of Arts and Science, Xiangyang, Hubei, People's Republic of China

  2. 2

    Department of Neurosurgery, University of Texas Heath Science Center at Houston, Houston, USA

  3. 3

    Department of Biochemistry and Molecular Medicine, Institute for Pediatric Regenerative Medicine, School of Medicine, University of California-Davis, Sacramento, CA 95817, USA

*Correspondence to: Wenbin Deng.

  1. Contract Grant Sponsor: National Institutes of Health.Contract Grant Numbers: R01 NS059043 and R01 ES015988.Contract Grant Sponsor: National Multiple Sclerosis Society.Contract Grant Sponsor: Roche Research Foundation.Contract Grant Sponsor: Alternatives Research and Development Foundation.Contract Grant Sponsor: Johns Hopkins Center for Alternatives to Animal Testing.Contract Grant Sponsor: University of California Toxic Substances Research and Teaching Program.Contract Grant Sponsor: Children's Miracle Network.Contract Grant Sponsor: Shriners Hospitals for Children.

  2. The authors declare no conflicts of interest.

Publication History

  1. Issue published online: 17 JAN 2013
  2. Article first published online: 4 JAN 2013
  3. Manuscript Accepted: 1 DEC 2012
  4. Manuscript Revised: 29 NOV 2012
  5. Manuscript Received: 23 JUL 2012

Funded by

  • National Institutes of Health. Grant Numbers: R01 NS059043, R01 ES015988
  • National Multiple Sclerosis Society
  • Roche Research Foundation
  • Alternatives Research and Development Foundation
  • Johns Hopkins Center for Alternatives to Animal Testing
  • University of California Toxic Substances Research and Teaching Program
  • Children's Miracle Network
  • Shriners Hospitals for Children

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Keywords:

  • Embryonic Stem Cell;
  • Iduced Pluripotent Stem Cell;
  • Drug Discovery;
  • Environmental Health Science;
  • Toxicity Testing

ABSTRACT

Human stem cells and their derivatives could provide virtually unlimited sources of tissue for a wide range of toxicity models that could complement conventional animal models with more relevant, humanized versions. Human embryonic stem cells (hESCs) have already been proven valuable for drug/toxicity screens and mechanistic studies including analysis of disease pathway and developmental toxicity. Human-induced pluripotent stem cells (iPSCs), which are generated by reprogramming somatic cells back to become hESC-like cells, allow assays to be designed where the contribution of an individual's genetic background or environmental exposure history to toxicity response can be determined. Comprehensive profiling of hESC/iPSCs via genomics, proteomics, transcriptomics, and metabolomics could be used to elucidate pathway perturbations that underlie toxicity and disease, enabling the development of predictive assays for toxicity. While technological hurdles still exist for widespread use and implementation, incorporation of human stem cell based assays into drug discovery and toxicity testing offers the potential for safer, more customized medicines and more accurate risk assessment for environmental toxicants, as well as reduced costs and decreased use of animal models. We examine limitations and deficiencies of current toxicology approaches and how human stem cell based in vitro assays may overcome them. We describe how human stem cells are used for predictive toxicology. We also identify technological limitations that prevent stem cells from being integrated into standard practice, as well as new tools and technologies that may overcome them. We discuss research priorities that are most useful for transforming cell-based toxicology models into reality, and research areas in which stem cell technology could make substantial contributions to the development and implementation of stem cell based models for toxicity testing. Increased use of human in vitro models of toxicity could reduce the use of animals in safety and risk assessment studies and offers the potential to dramatically enhance our understanding of the molecular basis of toxicity, leading to improved human models and assays for predicting biological response to drugs and environmental hazards. © 2012 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:17-27, 2013; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.21470

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