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Requirements for Using iPSC-Based Cell Models for Assay Development in Drug Discovery

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Engineering and Application of Pluripotent Stem Cells

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 163))

Abstract

A prevalent challenge in drug discovery is the translation of findings from preclinical research into clinical success. Currently, more physiological in vitro systems are being developed to overcome some of these challenges. In particular, induced pluripotent stem cells (iPSCs) have provided the opportunity to generate human cell types that can be utilized for developing more disease-relevant cellular assay models. As the use of these complex models is lengthy and fairly complicated, we lay out our experiences of the cultivation, differentiation, and quality control requirements to successfully utilize pluripotent stem cells in drug discovery.

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References

  1. Swinney DC, Anthony J (2011) How were new medicines discovered? Nat Rev Drug Discov 10:507–519. https://doi.org/10.1038/nrd3480

    Article  CAS  Google Scholar 

  2. Rees S, Gribbon P, Birmingham K, Janzen WP, Pairaudeau G (2016) Towards a hit for every target. Nat Rev Drug Discov 15:1–2. https://doi.org/10.1038/nrd.2015.19

    Article  CAS  Google Scholar 

  3. Horvath P et al. (2016) Screening out irrelevant cell-based models of disease. Nat Rev Drug Discov 15:751–769. https://doi.org/10.1038/nrd.2016.175

    Article  CAS  Google Scholar 

  4. Thomson JA et al. (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    Article  CAS  Google Scholar 

  5. Ciampi O et al. (2016) Generation of functional podocytes from human induced pluripotent stem cells. Stem Cell Res 17:130–139. https://doi.org/10.1016/j.scr.2016.06.001

    Article  CAS  Google Scholar 

  6. Patsch C et al. (2015) Generation of vascular endothelial and smooth muscle cells from human pluripotent stem cells. Nat Cell Biol 17:994–1003. https://doi.org/10.1038/ncb3205

    Article  CAS  Google Scholar 

  7. Tran TH et al. (2009) Wnt3a-induced mesoderm formation and cardiomyogenesis in human embryonic stem cells. Stem Cells 27:1869–1878. https://doi.org/10.1002/stem.95

    Article  CAS  Google Scholar 

  8. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676. https://doi.org/10.1016/j.cell.2006.07.024

    Article  CAS  Google Scholar 

  9. Takahashi K et al. (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872. https://doi.org/10.1016/j.cell.2007.11.019

    Article  CAS  Google Scholar 

  10. Musunuru K (2013) Genome editing of human pluripotent stem cells to generate human cellular disease models. Dis Model Mech 6:896–904. https://doi.org/10.1242/dmm.012054

    Article  CAS  Google Scholar 

  11. Ding Q et al. (2013) A TALEN genome-editing system for generating human stem cell-based disease models. Cell Stem Cell 12:238–251. https://doi.org/10.1016/j.stem.2012.11.011

    Article  CAS  Google Scholar 

  12. Ding Q et al. (2013) Enhanced efficiency of human pluripotent stem cell genome editing through replacing TALENs with CRISPRs. Cell Stem Cell 12:393–394. https://doi.org/10.1016/j.stem.2013.03.006

    Article  CAS  Google Scholar 

  13. Terstegge S et al. (2009) Laser-assisted selection and passaging of human pluripotent stem cell colonies. J Biotechnol 143:224–230. https://doi.org/10.1016/j.jbiotec.2009.07.002

    Article  CAS  Google Scholar 

  14. Ludwig TE et al. (2006) Derivation of human embryonic stem cells in defined conditions. Nat Biotechnol 24:185–187. https://doi.org/10.1038/nbt1177

    Article  CAS  Google Scholar 

  15. Mariotti E, Mirabelli P, Di Noto R, Fortunato G, Salvatore F (2008) Rapid detection of mycoplasma in continuous cell lines using a selective biochemical test. Leuk Res 32:323–326. https://doi.org/10.1016/j.leukres.2007.04.010

    Article  CAS  Google Scholar 

  16. Young L, Sung J, Stacey G, Masters JR (2010) Detection of mycoplasma in cell cultures. Nat Protoc 5:929–934. https://doi.org/10.1038/nprot.2010.43

    Article  CAS  Google Scholar 

  17. Muller FJ, Brandl B, Loring JF (2008) StemBook [Internet]. Harvard Stem Cell Institute, Cambridge. doi:https://doi.org/10.3824/stembook.1.84.1

  18. Adewumi O et al. (2007) Characterization of human embryonic stem cell lines by the international stem cell initiative. Nat Biotechnol 25:803–816. https://doi.org/10.1038/nbt1318

    Article  CAS  Google Scholar 

  19. Wiese C, Kania G, Rolletschek A, Blyszczuk P, Wobus AM (2006) Pluripotency: capacity for in vitro differentiation of undifferentiated embryonic stem cells. Methods Mol Biol 325:181–205. https://doi.org/10.1385/1-59745-005-7:181

    CAS  Google Scholar 

  20. Martins-Taylor K et al. (2011) Recurrent copy number variations in human induced pluripotent stem cells. Nat Biotechnol 29:488–491. https://doi.org/10.1038/nbt.1890

    Article  CAS  Google Scholar 

  21. Baker D et al. (2016) Detecting genetic mosaicism in cultures of human pluripotent stem cells. Stem Cell Rep 7:998–1012. https://doi.org/10.1016/j.stemcr.2016.10.003

    Article  CAS  Google Scholar 

  22. Taapken SM et al. (2011) Karotypic abnormalities in human induced pluripotent stem cells and embryonic stem cells. Nat Biotechnol 29:313–314. https://doi.org/10.1038/nbt.1835

    Article  CAS  Google Scholar 

  23. Avery S et al. (2013) BCL-XL mediates the strong selective advantage of a 20q11.21 amplification commonly found in human embryonic stem cell cultures. Stem Cell Rep 1:379–386. https://doi.org/10.1016/j.stemcr.2013.10.005

    Article  CAS  Google Scholar 

  24. Nguyen HT et al. (2014) Gain of 20q11.21 in human embryonic stem cells improves cell survival by increased expression of Bcl-xL. Mol Hum Reprod 20:168–177. https://doi.org/10.1093/molehr/gat077

    Article  CAS  Google Scholar 

  25. Liu P et al. (2014) Passage number is a major contributor to genomic structural variations in mouse iPSCs. Stem Cells 32:2657–2667. https://doi.org/10.1002/stem.1779

    Article  CAS  Google Scholar 

  26. Amps K et al. (2011) Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage. Nat Biotechnol 29:1132–1144. https://doi.org/10.1038/nbt.2051

    Article  CAS  Google Scholar 

  27. Kilpinen H et al. (2017) Common genetic variation drives molecular heterogeneity in human iPSCs. Nature 546:370–375. https://doi.org/10.1038/nature22403

    Article  CAS  Google Scholar 

  28. Scannell JW, Blanckley A, Boldon H, Warrington B (2012) Diagnosing the decline in pharmaceutical R&D efficiency. Nat Rev Drug Discov 11:191–200. https://doi.org/10.1038/nrd3681

    Article  CAS  Google Scholar 

  29. Mullard A (2015) Stem-cell discovery platforms yield first clinical candidates. Nat Rev Drug Discov 14:589–591. https://doi.org/10.1038/nrd4708

    Article  CAS  Google Scholar 

  30. Bright J et al. (2015) Human secreted tau increases amyloid-beta production. Neurobiol Aging 36:693–709. https://doi.org/10.1016/j.neurobiolaging.2014.09.007

    Article  CAS  Google Scholar 

  31. Chambers SM et al. (2009) Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 27:275–280. https://doi.org/10.1038/nbt.1529

    Article  CAS  Google Scholar 

  32. Costa V et al. (2016) mTORC1 inhibition corrects neurodevelopmental and synaptic alterations in a human stem cell model of tuberous sclerosis. Cell Rep 15:86–95. https://doi.org/10.1016/j.celrep.2016.02.090

    Article  CAS  Google Scholar 

  33. Dunkley T et al. (2015) Characterization of a human pluripotent stem cell-derived model of neuronal development using multiplexed targeted proteomics. Proteomics Clin Appl 9:684–694. https://doi.org/10.1002/prca.201400150

    Article  CAS  Google Scholar 

  34. Qi Y et al. (2017) Combined small-molecule inhibition accelerates the derivation of functional cortical neurons from human pluripotent stem cells. Nat Biotechnol 35:154–163. https://doi.org/10.1038/nbt.3777

    Article  CAS  Google Scholar 

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Acknowledgements

The authors acknowledge Silke Zimmermann, Nadine Dahm, and Corinne Marfing for technical assistance and Cecilia Cariño Morales for proof reading.

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Authors and Affiliations

  1. Roche pRED (Pharmaceutical Research and Early Development), Roche Innovation Center Basel, F.Hoffmann-La Roche Ltd., Basel, Switzerland

    Klaus Christensen, Filip Roudnicky, Christoph Patsch & Mark Burcin

Authors
  1. Klaus Christensen
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  2. Filip Roudnicky
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  3. Christoph Patsch
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  4. Mark Burcin
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Corresponding author

Correspondence to Mark Burcin .

Editor information

Editors and Affiliations

  1. Leibniz Research Labs for Biotechnology, Hannover Medical School (MHH), Hannover, Germany

    Ulrich Martin

  2. Leibniz Research Labs for Biotechnology, Hannover Medical School (MHH), Hannover, Germany

    Robert Zweigerdt

  3. Leibniz Research Labs for Biotechnology, Hannover Medical School (MHH), Hannover, Germany

    Ina Gruh

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Christensen, K., Roudnicky, F., Patsch, C., Burcin, M. (2017). Requirements for Using iPSC-Based Cell Models for Assay Development in Drug Discovery. In: Martin, U., Zweigerdt, R., Gruh, I. (eds) Engineering and Application of Pluripotent Stem Cells. Advances in Biochemical Engineering/Biotechnology, vol 163. Springer, Cham. https://doi.org/10.1007/10_2017_23

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