• Please log in or register to access this feature.

Mini-Review

You have free access to this content

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

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (184K)

REFERENCES

  • 1
    Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006;126(4):663–676.
  • 2
    Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007;131(5):861–872.
  • 3
    Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA. Induced pluripotent stem cell lines derived from human somatic cells. Science 2007;318(5858):1917–1920.
  • 4
    Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ. Reprogramming of human somatic cells to pluripotency with defined factors. Nature 2008;451(7175):141–146.
  • 5
    Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N, Yamanaka S. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 2008;26(1):101–106.
  • 6
    Selvaraj V, Jiang P, Chechneva O, Lo UG, Deng W. Differentiating human stem cells into neurons and glial cells for neural repair. Front Biosci 2012;17:65–89.
  • 7
    Liu Y, Jiang P, Deng W. OLIG gene targeting in human pluripotent stem cells for motor neuron and oligodendrocyte differentiation. Nat Protoc 2011;6(5):640–655.
  • 8
    Selvaraj V, Plane JM, Williams AJ, Deng W. Switching cell fate: the remarkable rise of induced pluripotent stem cells and lineage reprogramming technologies. Trends Biotechnol 2010;28(4):214–223.
  • 9
    Deng W. Induced pluripotent stem cells: paths to new medicines. A catalyst for disease modelling, drug discovery and regenerative therapy. EMBO Rep 2010;11(3):161–165.
  • 10
    Kumar N, Sharma U, Singh C, Singh B. Thalidomide: chemistry, therapeutic potential and oxidative stress induced teratogenicity. Curr Top Med Chem 2012;12(13):1436–1455.
  • 11
    Ponce RA. Safety assessment of immunomodulatory biologics: the promise and challenges of regulatory T-cell modulation. J Immunotoxicol 2011;8(4):389–397.
  • 12
    Wang Y, Cui CB, Yamauchi M, Miguez P, Roach M, Malavarca R, Costello MJ, Cardinale V, Wauthier E, Barbier C, Gerber DA, Alvaro D, Reid LM. Lineage restriction of human hepatic stem cells to mature fates is made efficient by tissue-specific biomatrix scaffolds. Hepatology 2011;53(1):293–305.
    Direct Link:
  • 13
    Gong G, Roach ML, Jiang L, Yang X, Tian XC. Culture conditions and enzymatic passaging of bovine ESC-like cells. Cell Reprogram 2010;12(2):151–160.
  • 14
    Jiang J, Au M, Lu K, Eshpeter A, Korbutt G, Fisk G, Majumdar AS. Generation of insulin-producing islet-like clusters from human embryonic stem cells. Stem Cells 2007;25(8):1940–1953.
    Direct Link:
  • 15
    Nalos L, Varkevisser R, Jonsson MK, Houtman MJ, Beekman JD, van der Nagel R, Thomsen MB, Duker G, Sartipy P, de Boer TP, Peschar M, Rook MB, van Veen TA, van der Heyden MA, Vos MA. Comparison of the IKr blockers moxifloxacin, dofetilide and E-4031 in five screening models of pro-arrhythmia reveals lack of specificity of isolated cardiomyocytes. Br J Pharmacol 2012;165(2):467–478.
    Direct Link:
  • 16
    Okita K, Nakagawa M, Hyenjong H, Ichisaka T, Yamanaka S. Generation of mouse induced pluripotent stem cells without viral vectors. Science 2008;322(5903):949–953.
  • 17
    Yu J, Hu K, Smuga-Otto K, Tian S, Stewart R, Slukvin II, Thomson JA. Human induced pluripotent stem cells free of vector and transgene sequences. Science 2009;324(5928):797–801.
  • 18
    Stadtfeld M, Nagaya M, Utikal J, Weir G, Hochedlinger K. Induced pluripotent stem cells generated without viral integration. Science 2008;322(5903):945–949.
  • 19
    Ban H, Nishishita N, Fusaki N, Tabata T, Saeki K, Shikamura M, Takada N, Inoue M, Hasegawa M, Kawamata S, Nishikawa S. Efficient generation of transgene-free human induced pluripotent stem cells (iPSCs) by temperature-sensitive Sendai virus vectors. Proc Natl Acad Sci U S A 2011;108(34):14234–14239.
  • 20
    Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hämäläinen R, Cowling R, Wang W, Liu P, Gertsenstein M, Kaji K, Sung HK, Nagy A. piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 2009;458(7239):766–770.
  • 21
    Kaji K, Norrby K, Paca A, Mileikovsky M, Mohseni P, Woltjen K. Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature. 2009;458(7239):771–775.
  • 22
    Soldner F, Hockemeyer D, Beard C, Gao Q, Bell GW, Cook EG, Hargus G, Blak A, Cooper O, Mitalipova M, Isacson O, Jaenisch R. Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 2009;136(5):964–977.
  • 23
    Zhou H, Wu S, Joo JY, Zhu S, Han DW, Lin T, Trauger S, Bien G, Yao S, Zhu Y, Siuzdak G, Schöler HR, Duan L, Ding S. Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 2009;4(5):381–384.
  • 24
    Kim D, Kim CH, Moon JI, Chung YG, Chang MY, Han BS, Ko S, Yang E, Cha KY, Lanza R, Kim KS. Generation of human induced pluripotent stem cells by direct delivery of reprogramming proteins. Cell Stem Cell 2009;4(6):472–476.
  • 25
    Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, Kim J, Aryee MJ, Ji H, Ehrlich LI, Yabuuchi A, Takeuchi A, Cunniff KC, Hongguang H, McKinney-Freeman S, Naveiras O, Yoon TJ, Irizarry RA, Jung N, Seita J, Hanna J, Murakami P, Jaenisch R, Weissleder R, Orkin SH, Weissman IL, Feinberg AP, Daley GQ. Epigenetic memory in induced pluripotent stem cells. Nature 2010;467(7313):285–290.
  • 26
    Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack AS, Collins JJ, Cowan C, Schlaeger TM, Rossi DJ. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 2010;7(5):618–630.
  • 27
    Anokye-Danso F, Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, Zhang Y, Yang W, Gruber PJ, Epstein JA, Morrisey EE. Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell 2011;8(4):376–388.
  • 28
    Miyoshi N, Ishii H, Nagano H, Haraguchi N, Dewi DL, Kano Y, Nishikawa S, Tanemura M, Mimori K, Tanaka F, Saito T, Nishimura J, Takemasa I, Mizushima T, Ikeda M, Yamamoto H, Sekimoto M, Doki Y, Mori M. Reprogramming of mouse and human cells to pluripotency using mature microRNAs. Cell Stem Cell 2011;8(6):633–638.
  • 29
    Rubin LL. Stem cells and drug discovery: the beginning of a new era? Cell 2008;132(4):549–552.
  • 30
    Mueller D, Tascher G, Müller-Vieira U, Knobeloch D, Nuessler AK, Zeilinger K, Heinzle E, Noor F. In-depth physiological characterization of primary human hepatocytes in a 3D hollow-fiber bioreactor. J Tissue Eng Regen Med 2011;5(8):e207–e218.
    Direct Link:
  • 31
    Huang S. Systems biology of stem cells: three useful perspectives to help overcome the paradigm of linear pathways. Philos Trans R Soc Lond B: Biol Sci 2011;366(1575):2247–2259.
  • 32
    Jiang P, Rushing SN, Kong CW, Fu J, Lieu DK, Chan CW, Deng W, Li RA. Electrophysiological properties of human induced pluripotent stem cells. Am J Physiol Cell Physiol 2010;298(3):C486–C495.
  • 33
    Heinrich C, Gascón S, Masserdotti G, Lepier A, Sanchez R, Simon-Ebert T, Schroeder T, Götz M, Berninger B. Generation of subtype-specific neurons from postnatal astroglia of the mouse cerebral cortex. Nat Protoc 2011;6(2):214–228.
  • 34
    Coyne L, Shan M, Przyborski SA, Hirakawa R, Halliwell RF. Neuropharmacological properties of neurons derived from human stem cells. Neurochem Int 2011;59(3):404–412.
  • 35
    Li H, Liu H, Corrales CE, Risner JR, Forrester J, Holt JR, Heller S, Edge AS. Differentiation of neurons from neural precursors generated in floating spheres from embryonic stem cells. BMC Neurosci 2009;10:122.
  • 36
    Deng W. Neurobiology of injury to the developing brain. Nat Rev Neurol 2010;6(6):328–336.
  • 37
    Deng W, Neve RL, Rosenberg PA, Volpe JJ, Jensen FE. AMPA receptor composition and CREB regulate oligodendrocyte excitotoxicity. J Biol Chem 2006;281:36004–36011.
  • 38
    Deng W, Yue Q, Rosenberg PA, Volpe JJ, Jensen FE. Oligodendrocyte excitotoxicity determined by local glutamate accumulation and mitochondrial function. J Neurochem 2006;98:213–222.
    Direct Link:
  • 39
    Deng W, Wang H, Rosenberg PA, Volpe JJ, Jensen FE. Role of metabotropic glutamate receptors in oligodendrocyte excitotoxicity and oxidative stress. Proc Natl Acad Sci USA 2004;101:7751–7756.
  • 40
    Follett PL, Deng W, Talos D, Massillon L, Rosenberg PA, Volpe JJ, Jensen FE. Glutamate receptor-mediated oligodendrocyte toxicity in periventricular leukomalacia: a protective role for topiramate. J Neurosci 2004;24:4412–4420.
  • 41
    Deng W, Rosenberg PA, Volpe JJ, Jensen FE. Calcium-permeable AMPA/kainate receptors mediate toxicity and preconditioning by oxygen-glucose deprivation in oligodendrocyte precursors. Proc Natl Acad Sci USA 2003;100:6801–6806.
  • 42
    Deng W, Poretz RD. Oligodendroglia in developmental neurotoxicity. Neurotoxicology 2003;24:161–178.
  • 43
    Deng W, Poretz RD. Protein kinase C activation is required for the lead-induced inhibition of proliferation and differentiation of cultured oligodendroglial progenitor cells. Brain Res 2002;929:87–95.
  • 44
    Deng W, Poretz RD. Chronic dietary lead exposure affects galactolipid metabolic enzymes in the developing rat brain. Toxicol Appl Pharmacol 2001;172:98–107.
  • 45
    Deng W, McKinnon RD, Poretz RD. Lead exposure delays the differentiation of oligodendroglial progenitors in vitro. Toxicol Appl Pharmacol 2001;174:235–244.
  • 46
    Deng W, Poretz RD. Lead alters the developmental profile of galactolipid metabolic enzymes in cultured oligodendrocyte lineage cells. Neurotoxicology 2001;22:429–437.
  • 47
    Hussein SM, Elbaz J, Nagy AA. Genome damage in induced pluripotent stem cells: Assessing the mechanisms and their consequences. Bioessays 2012. doi: 10.1002/bies.201200114.
    Direct Link:
  • 48
    Lin HT, Otsu M, Nakauchi H. Stem cell therapy: an exercise in patience and prudence. Philos Trans R Soc Lond B Biol Sci 2013;368 (1609): 20110334.
  • 49
    Fu X, Xu Y. Challenges to the clinical application of pluripotent stem cells: towards genomic and functional stability. Genome Med 2012;4(6):55.
  • 50
    Tobin SC, Kim K. Generating pluripotent stem cells: differential epigenetic changes during cellular reprogramming. FEBS Lett 2012;586(18):2874–2881.
  • 51
    Deng W, Xu Y. Genome integrity: linking pluripotency and tumorgenicity. Trends Genet 2009;25(10):425–427.
  • 52
    Deng W. PARylation: strengthening the connection between cancer and pluripotency. Cell Stem Cell 2009;5(4):349–350.
  • 53
    Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, Kim J, Aryee MJ, Ji H, Ehrlich LI, Yabuuchi A, Takeuchi A, Cunniff KC, Hongguang H, McKinney-Freeman S, Naveiras O, Yoon TJ, Irizarry RA, Jung N, Seita J, Hanna J, Murakami P, Jaenisch R, Weissleder R, Orkin SH, Weissman IL, Feinberg AP, Daley GQ. Epigenetic memory in induced pluripotent stem cells. Nature 2010;467(7313):285–290.
  • 54
    Kim K, Zhao R, Doi A, Ng K, Unternaehrer J, Cahan P, Huo H, Loh YH, Aryee MJ, Lensch MW, Li H, Collins JJ, Feinberg AP, Daley GQ. Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells. Nat Biotechnol 2011;29(12):1117–1119.
  • 55
    Xu Y, Shi Y, Ding S. A chemical approach to stem-cell biology and regenerative medicine. Nature 2008;453(7193):338–344
  • 56
    Hanna JH, Saha K, Jaenisch R. Pluripotency and cellular reprogramming: facts, hypotheses, unresolved issues. Cell 2010;143(4):508–525.
View Full Article (HTML) Get PDF (184K)