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Pluripotent Human Stem Cells

A Novel Tool in Drug Discovery

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Abstract

The need for new and improved pharmacotherapies in medicine, high late-stage compound attrition in drug discovery, and upcoming patent expirations is driving interest by the pharmaceutical industry in pluripotent stem cells for in vitro modeling and early-stage testing of toxicity and target engagement. In particular, human embryonic and induced pluripotent stem cells represent potentially cost-effective and accessible sources of organ-specific cells that foretell in vivo human tissue response to new chemical entities. Here we consider the potential of these cells as novel tools for drug development, including toxicity screening and metabolic profiling. We hold that despite various challenges to translating proof-of-concept screening platforms to industrial use, the promise of research is considerable, and close to being realized.

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References

  1. DiMasi JA, Hansen RW, Grabowski HG. The price of innovation: new estimates of drug development costs. J Health Econ 2003 Mar; 22(2): 151–85

    Article  PubMed  Google Scholar 

  2. Collier R. Drug development cost estimates hard to swallow. CMAJ 2009 Feb 3; 180(3): 279–80

    Article  PubMed  Google Scholar 

  3. Booth B, Zemmel R. Prospects for productivity. Nat Rev Drug Discov 2004 May; 3(5): 451–6

    Article  PubMed  CAS  Google Scholar 

  4. Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 2004 Aug; 3(8): 711–5

    Article  PubMed  CAS  Google Scholar 

  5. Schafer S, Kolkhof P. Failure is an option: learning from unsuccessful proof-of-concept trials. Drug Discov Today 2008 Nov; 13(21–22): 913–6

    Article  PubMed  Google Scholar 

  6. Gomez-Lechon MJ, Castell JV, Donato MT. An update on metabolism studies using human hepatocytes in primary culture. Expert Opin Drug Metab Toxicol 2008 Jul; 4(7): 837–54

    Article  PubMed  CAS  Google Scholar 

  7. Uchida N, Buck DW, He D, et al. Direct isolation of human central nervous system stem cells. Proc Natl Acad Sci U S A 2000 Dec 19; 97(26): 14720–5

    Article  PubMed  CAS  Google Scholar 

  8. Kelly HT, Hill E, Reid F, et al. Comparison of RAP-PCR analysis of gene expression in fresh and immortalised rat hepatocyte cell lines. Cytotechnology 2000 Oct; 34(1–2): 159–63

    Article  PubMed  CAS  Google Scholar 

  9. Nirmalanandhan VS, Sittampalam GS. Stem cells in drug discovery, tissue engineering, and regenerative medicine: emerging opportunities and challenges. J Biomol Screen 2009 Aug 12; 14(7): 755–68

    Article  PubMed  CAS  Google Scholar 

  10. Keller G. Embryonic stem cell differentiation: emergence of a new era in biology and medicine. Genes Dev 2005 May 15; 19(10): 1129–55

    Article  PubMed  CAS  Google Scholar 

  11. Nishikawa SI, Goldstein RA, Nierras CR. The promise of human induced pluripotent stem cells for research and therapy. Nat Rev Mol Cell Biol 2008 Sept; 9(9): 725–9

    Article  PubMed  CAS  Google Scholar 

  12. Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007 Nov 30; 131(5): 861–72

    Article  PubMed  CAS  Google Scholar 

  13. Maherali N, Sridharan R, Xie W, et al. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 2007 Jun 7; 1(1): 55–70

    Article  PubMed  CAS  Google Scholar 

  14. Zhao XY, Li W, Lv Z, et al. iPS cells produce viable mice through tetraploid complementation. Nature 2009 Sep 3; 461(7260): 86–90

    Article  PubMed  CAS  Google Scholar 

  15. Boland MJ, Hazen JL, Nazor KL, et al. Adult mice generated from induced pluripotent stem cells. Nature 2009 Sep 3; 61(7260): 91–4

    Article  Google Scholar 

  16. Bongso A, Fong CY, Ng SC, et al. Human embryonic behavior in a sequential human oviduct-endometrial coculture system. Fertil Steril 1994 May; 61(5): 976–8

    PubMed  CAS  Google Scholar 

  17. Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Embryonic stem cell lines derived from human blastocysts. Science 1998 Nov 6; 282(5391): 1145–7

    Article  PubMed  CAS  Google Scholar 

  18. Phillips BW, Hentze H, Rust WL, et al. Directed differentiation of human embryonic stem cells into the pancreatic endocrine lineage. Stem Cells Dev 2007; 16: 561–78

    Article  PubMed  CAS  Google Scholar 

  19. Xu XQ, Zweigerdt R, Soo SY, et al. Highly enriched cardiomyocytes from human embryonic stem cells. Cytotherapy 2008; 10(4): 376–89

    Article  PubMed  Google Scholar 

  20. Cho MS, Lee YE, Kim JY, et al. Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells. Proc Natl Acad Sci U S A 2008 Mar 4; 105(9): 3392–7

    Article  PubMed  CAS  Google Scholar 

  21. Zou J, Maeder ML, Mali P, et al. Gene targeting of a disease-related gene in human induced pluripotent stem and embryonic stem cells. Cell Stem Cell 2009 Jul 2; 5(1): 97–110

    Article  PubMed  CAS  Google Scholar 

  22. Nakagawa M, Koyanagi M, Tanabe K, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol 2008 Jan; 26(1): 101–6

    Article  PubMed  CAS  Google Scholar 

  23. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006 Aug; 8(126): 1–4

    Google Scholar 

  24. Kim JB, Zaehres H, Wu G, et al. Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors. Nature 2008 Jul 31; 454(7204): 646–50

    Article  PubMed  CAS  Google Scholar 

  25. Miura K, Okada Y, Aoi T, et al. Variation in the safety of induced pluripotent stem cell lines. Nat Biotechnol 2009 Aug; 27(8): 743–5

    Article  PubMed  CAS  Google Scholar 

  26. Huangfu D, Maehr R, Guo W, et al. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol 2008 Jul; 26(7): 795–7

    Article  PubMed  CAS  Google Scholar 

  27. Yu J, Hu K, Smuga-Otto K, et al. Human induced pluripotent stem cells free of vector and transgene sequences. Science 2009 May 8; 324(5928): 797–801

    Article  PubMed  CAS  Google Scholar 

  28. Woltjen K, Michael IP, Mohseni P, et al. piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 2009 Apr 9; 458(7239): 766–70

    Article  PubMed  CAS  Google Scholar 

  29. Kaji K, Norrby K, Paca A, et al. Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature 2009 Apr 9; 458(7239): 771–5

    Article  PubMed  CAS  Google Scholar 

  30. Pal R, Totey SS, Mamidi MK, et al. Propensity of human embryonic stem cell lines during early stage of lineage specification control their terminal differentiation into mature cell types. Exp Biol Med (Maywood) 2009 Oct; 234(10): 1230–43

    Article  CAS  Google Scholar 

  31. Osafune K, Caron L, Borowiak M, et al. Marked differences in differentiation propensity among human embryonic stem cell lines. Nat Biotechnol 2008 Mar; 26(3): 313–5

    Article  PubMed  CAS  Google Scholar 

  32. Chin MH, Mason MJ, Xie W, et al. Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell 2009 Jul 2; 5(1): 111–23

    Article  PubMed  CAS  Google Scholar 

  33. Park IH, Arora N, Huo H, et al. Disease-specific induced pluripotent stem cells. Cell 2008 Sep 5; 134(5): 877–86

    Article  PubMed  CAS  Google Scholar 

  34. Dimos JT, Rodolfa KT, Niakan KK, et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 2008 Aug 29; 321(5893): 1218–21

    Article  PubMed  CAS  Google Scholar 

  35. Keseru GM, Makara GM. The influence of lead discovery strategies on the properties of drug candidates. Nat Rev Drug Discov 2009 Mar; 8(3): 203–12

    Article  PubMed  Google Scholar 

  36. Guguen-Guillouzo C, Corlu A, Guillouzo A. Stem cell-derived hepatocytes and their use in toxicology. Toxicology. Epub 2009 Oct 6

  37. Gomez-Lechon MJ, Castell JV, Donato MT. Hepatocytes: the choice to investigate drug metabolism and toxicity in man: in vitro variability as a reflection of in vivo. Chem Biol Interact 2007 May 20; 168(1): 30–50

    Article  PubMed  CAS  Google Scholar 

  38. Soars MG, McGinnity DF, Grime K, et al. The pivotal role of hepatocytes in drug discovery. Chem Biol Interact 2007 May 20; 168(1): 2–15

    Article  PubMed  CAS  Google Scholar 

  39. O’Brien PJ, Chan K, Silber PM. Human and animal hepatocytes in vitro with extrapolation in vivo. Chem Biol Interact 2004 Nov 1; 150(1): 97–114

    Article  PubMed  Google Scholar 

  40. Borowiak M, Maehr R, Chen S, et al. Small molecules efficiently direct endodermal differentiation of mouse and human embryonic stem cells. Cell Stem Cell 2009 Apr 3; 4(4): 348–58

    Article  PubMed  CAS  Google Scholar 

  41. Suter DM, Preynat-Seauve O, Tirefort D, et al. Phenazopyridine induces and synchronizes neuronal differentiation of embryonic stem cells. J Cell Mol Med. Epub 2009 Jan 16

  42. Desbordes SC, Placantonakis DG, Ciro A, et al. High-throughput screening assay for the identification of compounds regulating self-renewal and differentiation in human embryonic stem cells. Cell Stem Cell 2008 Jun 5; 2(6): 602–12

    Article  PubMed  CAS  Google Scholar 

  43. Frantz S. How to avoid another ‘Vioxx’. Nat Rev Drug Discov 2005 Jan; 4(1): 5–7

    Article  PubMed  CAS  Google Scholar 

  44. Greener M. Drug safety on trial. Last year’s withdrawal of the anti-arthritis drug Vioxx triggered a debate about how to better monitor drug safety even after approval. EMBO Rep 2005 Mar; 6(3): 202–4

    Article  PubMed  CAS  Google Scholar 

  45. Dessertenne F. Ventricular tachycardia with 2 variable opposing foci. Arch Mal Coeur Vaiss 1966 Feb; 59(2): 263–72

    PubMed  CAS  Google Scholar 

  46. Soubret A, Helmlinger G, Dumotier B, et al. Modeling and simulation of preclinical cardiac safety: towards an integrative framework. Drug Metab Pharmacokinet 2009; 24(1): 76–90

    Article  PubMed  CAS  Google Scholar 

  47. Thomsen MB, Matz J, Volders PG, et al. Assessing the proarrhythmic potential of drugs: current status of models and surrogate parameters of torsades de pointes arrhythmias. Pharmacol Ther 2006 Oct; 112(1): 150–70

    Article  PubMed  CAS  Google Scholar 

  48. Sanguinetti MC, Jiang C, Curran ME, et al. A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 1995 Apr 21; 81(2): 299–307

    Article  PubMed  CAS  Google Scholar 

  49. Hanton G, Tilbury L. Cardiac safety strategies: 25–26 October 2005, the Radisson SAS Hotel, Nice, France. Expert Opin Drug Saf 2006 Mar; 5(2): 329–33

    Article  PubMed  CAS  Google Scholar 

  50. Mummery C, Ward-van Oostwaard D, Doevendans P, et al. Differentiation of human embryonic stem cells to cardiomyocytes: role of coculture with visceral endoderm-like cells. Circulation 2003 Jun 3; 107(21): 2733–40

    Article  PubMed  CAS  Google Scholar 

  51. Xu XQ, Graichen R, Soo SY, et al. Chemically defined medium supporting cardiomyocyte differentiation of human embryonic stem cells. Differentiation 2008 Nov; 76(9): 958–70

    PubMed  CAS  Google Scholar 

  52. Passier R, Oostwaard DW, Snapper J, et al. Increased cardiomyocyte differentiation from human embryonic stem cells in serum-free cultures. Stem Cells 2005 Jun–Jul; 23(6): 772–80

    Article  PubMed  CAS  Google Scholar 

  53. Graichen R, Xu X, Braam SR, et al. Enhanced cardiomyogenesis of human embryonic stem cells by a small molecular inhibitor of p38 MAPK. Differentiation 2007 Nov 15; 76(4): 357–70

    Article  PubMed  Google Scholar 

  54. He JQ, January CT, Thomson JA, Kamp TJ. Human embryonic stem cell-derived cardiomyocytes: drug discovery and safety pharmacology. Exp Opin Drug Discov 2007; 2(5): 739–53

    Article  CAS  Google Scholar 

  55. He JQ, Ma Y, Lee Y, et al. Human embryonic stem cells develop into multiple types of cardiac myocytes: action potential characterization. Circ Res 2003 Jul 11; 93(1): 32–9

    Article  PubMed  CAS  Google Scholar 

  56. Zhang J, Wilson GF, Soerens AG, et al. Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res 2009 Feb 27; 104(4): e30–41

    Article  PubMed  CAS  Google Scholar 

  57. Yokoo N, Baba S, Kaichi S, et al. The effects of cardioactive drugs on cardiomyocytes derived from human induced pluripotent stem cells. Biochem Biophys Res Commun 2009 Sep 25; 387(3): 482–8

    Article  PubMed  CAS  Google Scholar 

  58. Park MV, Annema W, Salvati A, et al. In vitro developmental toxicity test detects inhibition of stem cell differentiation by silica nanoparticles. Toxicol Appl Pharmacol 2009 Oct 1; 240(1): 108–16

    Article  PubMed  CAS  Google Scholar 

  59. Adler S, Pellizzer C, Hareng L, et al. First steps in establishing a developmental toxicity test method based on human embryonic stem cells. Toxicol In Vitro 2008 Feb; 22(1): 200–11

    Article  PubMed  CAS  Google Scholar 

  60. Abdul Kadir SH, Ali NN, Mioulane M, et al. Embryonic stem cell-derived cardiomyocytes as a model to study fetal arrhythmia related to maternal disease. J Cell Mol Med. Epub 2009 Mar 6

  61. Zhou SF, Liu JP, Chowbay B. Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab Rev 2009; 41(2): 89–295

    Article  PubMed  CAS  Google Scholar 

  62. Itskovitz-Eldor J, Schuldiner M, Karsenti D, et al. Differentiation of human embryonic stem cells into embryoid bodies compromising the three embryonic germ layers. Mol Med 2000 Feb; 6(2): 88–95

    PubMed  CAS  Google Scholar 

  63. Schuldiner M, Yanuka O, Itskovitz-Eldor J, et al. Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A 2000 Oct 10; 97(21): 11307–12

    Article  PubMed  CAS  Google Scholar 

  64. Rambhatla L, Chiu CP, Kundu P, et al. Generation of hepatocyte-like cells from human embryonic stem cells. Cell Transplant 2003; 12(1): 1–11

    Article  PubMed  Google Scholar 

  65. Lavon N, Yanuka O, Benvenisty N. Differentiation and isolation of hepatic-like cells from human embryonic stem cells. Differentiation 2004 Jun; 72(5): 230–8

    Article  PubMed  CAS  Google Scholar 

  66. Hay DC, Fletcher J, Payne C, et al. Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling. Proc Natl Acad Sci U S A 2008 Aug 26; 105(34): 12301–6

    Article  PubMed  CAS  Google Scholar 

  67. Basma H, Soto-Gutierrez A, Yannam GR, et al. Differentiation and transplantation of human embryonic stem cell-derived hepatocytes. Gastroenterology 2009 Mar; 136(3): 990–9

    Article  PubMed  CAS  Google Scholar 

  68. Zwaka TP, Thomson JA. Homologous recombination in human embryonic stem cells. Nat Biotechnol 2003 Mar; 21(3): 319–21

    Article  PubMed  CAS  Google Scholar 

  69. Xia X, Zhang SC. Genetic modification of human embryonic stem cells. Biotechnol Genet Eng Rev 2007; 24: 297–309

    PubMed  CAS  Google Scholar 

  70. Braam SR, Denning C, van den Brink S, et al. Improved genetic manipulation of human embryonic stem cells. Nat Methods 2008 May; 5(5): 389–92

    Article  PubMed  CAS  Google Scholar 

  71. Costa M, Dottori M, Ng E, et al. The hESC line Envy expresses high levels of GFP in all differentiated progeny. Nat Methods 2005 Mar 23; 2(4): 259–60

    Article  PubMed  CAS  Google Scholar 

  72. Costa M, Dottori M, Sourris K, et al. A method for genetic modification of human embryonic stem cells using electroporation. Nat Protoc 2007; 2(4): 792–6

    Article  PubMed  CAS  Google Scholar 

  73. Cabaniols JP, Mathis L, Delenda C. Targeted gene modifications in drug discovery and development. Curr Opin Pharmacol 2009 Oct; 9(5): 657–63

    Article  PubMed  CAS  Google Scholar 

  74. Andrews PW. Response: karyotype of human ES cells during extended culture [letter]. Nat Biotechnol 2004 Apr; 22(4): 382

    Article  CAS  Google Scholar 

  75. Dhara SK, Gerwe BA, Majumder A, et al. Genetic manipulation of neural progenitors derived from human embryonic stem cells. Tissue Eng Part A 2009 Nov; 15(11): 3621–34

    Article  PubMed  CAS  Google Scholar 

  76. Kobayashi NR, Sui L, Tan SL, et al. Modelling disrupted-in-schizophremia 1 loss of function in human neural progenitor cells: tools for molecular studies of human neurodevelopment and neuropsychiatric disorders. Mol Psyc. Epub 2009 Dec 15

  77. Verlinsky Y, Strelchenko N, Kukharenko V, et al. Human embryonic stem cell lines with genetic disorders. Reprod Biomed Online 2005 Jan; 10(1): 105–10

    Article  PubMed  CAS  Google Scholar 

  78. Niclis JC, Trounson AO, Dottori M, et al. Human embryonic stem cell models of Huntington disease. Reprod Biomed Online 2009 Jul; 19(1): 106–13

    Article  PubMed  CAS  Google Scholar 

  79. Eiges R, Urbach A, Malcov M, et al. Developmental study of fragile X syndrome using human embryonic stem cells derived from preimplantation genetically diagnosed embryos. Cell Stem Cell 2007 Nov; 1(5): 568–77

    Article  PubMed  CAS  Google Scholar 

  80. Belmonte JC, Ellis J, Hochedlinger K, et al. Induced pluripotent stem cells and reprogramming: seeing the science through the hype. Nat Rev Genet 2009 Dec; 10(12): 878–83

    Article  Google Scholar 

  81. Abeliovich A, Doege CA. Reprogramming therapeutics: iPS cell prospects for neurodegenerative disease. Neuron 2009 Feb 12; 61(3): 337–9

    Article  PubMed  CAS  Google Scholar 

  82. Maehr R, Chen S, Snitow M, et al. Generation of pluripotent stem cells from patients with type 1 diabetes. Proc Natl Acad Sci U S A 2009 Sep 15; 106(37): 15768–73

    Article  PubMed  CAS  Google Scholar 

  83. Ebert AD, Yu J, Rose Jr FF, et al. Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 2009 Jan 15; 457(7227): 277–80

    Article  PubMed  CAS  Google Scholar 

  84. Lee G, Papapetrou EP, Kim H, et al. Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 2009 Sep 17; 461(7262): 402–6

    Article  PubMed  CAS  Google Scholar 

  85. Brichta L, Hofmann Y, Hahnen E, et al. Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy. Hum Mol Genet 2003 Oct 1; 12(19): 2481–9

    Article  PubMed  CAS  Google Scholar 

  86. Cuajungco MP, Leyne M, Mull J, et al. Tissue-specific reduction in splicing efficiency of IKBKAP due to the major mutation associated with familial dysautonomia. Am J Hum Genet 2003 Mar; 72(3): 749–58

    Article  PubMed  CAS  Google Scholar 

  87. Mollamohammadi S, Taei A, Pakzad M, et al. A simple and efficient cryopreservation method for feeder-free dissociated human induced pluripotent stem cells and human embryonic stem cells. Hum Reprod 2009 Oct; 24(10): 2468–76

    Article  PubMed  CAS  Google Scholar 

  88. Phillips BW, Horne R, Lay TS, et al. Attachment and growth of human embryonic stem cells on microcarriers. J Biotechnol 2008 Nov 6; 138(1–2): 24–32

    Article  PubMed  CAS  Google Scholar 

  89. Lock LT, Tzanakakis ES. Expansion and differentiation of human embryonic stem cells to endoderm progeny in a microcarrier stirred-suspension culture. Tissue Eng Part A 2009 Aug; 15(8): 2051–63

    Article  PubMed  CAS  Google Scholar 

  90. Nie Y, Bergendahl V, Hei DJ, et al. Scalable culture and cryopreservation of human embryonic stem cells on microcarriers. Biotechnol Prog 2009 Jan–Feb; 25(1): 20–31

    Article  PubMed  CAS  Google Scholar 

  91. Oh SK, Chen AK, Mok Y, et al. Long-term microcarrier suspension cultures of human embryonic stem cells. Stem Cell Res. Epub 2009 Mar 4

  92. Fernandes AM, Marinho PA, Sartore RC, et al. Successful scale-up of human embryonic stem cell production in a stirred microcarrier culture system. Braz J Med Biol Res 2009 Jun; 42(6): 515–22

    Article  PubMed  CAS  Google Scholar 

  93. Levenstein ME, Ludwig TE, Xu RH, et al. Basic FGF support of human embryonic stem cell self-renewal. Stem Cells 2006 Nov 10; 24(3): 568–74

    Article  PubMed  CAS  Google Scholar 

  94. Amit M, Shariki C, Margulets V, et al. Feeder layer- and serum-free culture of human embryonic stem cells. Biol Reprod 2004; 70(3): 837–45

    Article  PubMed  CAS  Google Scholar 

  95. Ding V, Choo AB, Oh SK. Deciphering the importance of three key media components in human embryonic stem cell cultures. Biotechnol Lett 2006 Apr; 28(7): 491–5

    Article  PubMed  CAS  Google Scholar 

  96. Phillips BW, Lim RY, Tan TT, et al. Efficient expansion of clinical-grade human fibroblasts on microcarriers: cells suitable for ex vivo expansion of clinical-grade hESCs. J Biotechnol 2008 Mar 20; 134(1–2): 79–87

    Article  PubMed  CAS  Google Scholar 

  97. Bajpai R, Lesperance J, Kim M, et al. Efficient propagation of single cells accutase-dissociated human embryonic stem cells. Mol Reprod Dev 2007 Dec 21; 75(5): 818–27

    Article  Google Scholar 

  98. Hasegawa K, Fujioka T, Nakamura Y, et al. A method for the selection of human embryonic stem cell sublines with high replating efficiency after single-cell dissociation. Stem Cells 2006 Dec; 24(12): 2649–60

    Article  PubMed  CAS  Google Scholar 

  99. Ellerstrom C, Strehl R, Noaksson K, et al. Facilitated expansion of human embryonic stem cells by single cell enzymatic dissociation. Stem Cells 2007 Mar 22; 25(7): 1690–6

    Article  PubMed  Google Scholar 

  100. Baker DE, Harrison NJ, Maltby E, et al. Adaptation to culture of human embryonic stem cells and oncogenesis in vivo. Nat Biotechnol 2007 Feb; 25(2): 207–15

    Article  PubMed  CAS  Google Scholar 

  101. Watanabe K, Ueno M, Kamiya D, et al. A ROCK inhibitor permits survival of dissociated human embryonic stem cells. Nat Biotechnol 2007 Jun; 25(6): 681–6

    Article  PubMed  CAS  Google Scholar 

  102. Crook JM, Peura TT, Kravets L, et al. The generation of six clinical-grade human embryonic stem cell lines. Cell Stem Cell 2007; 1(5): 490–4

    Article  CAS  Google Scholar 

  103. Maddox CB, Rasmussen L, White EL. Adapting cell-based assays to the high throughput screening platform: problems encountered and lessons learned. JALA Charlottesv Va 2008 Jun; 13(3): 168–73

    PubMed  Google Scholar 

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Acknowledgments

The authors wish to thank the Helen Macpherson Smith Trust and O’Brien Foundation for supporting the writing of this manuscript.

The authors have no conflict of interests that are directly relevant to the content of this review.

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Correspondence to Jeremy M. Crook.

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Phillips, B.W., Crook, J.M. Pluripotent Human Stem Cells. BioDrugs 24, 99–108 (2010). https://doi.org/10.2165/11532270-000000000-00000

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