Skip to main content
SpringerLink
Log in
Book cover

Medical Applications of iPS Cells pp 3–12Cite as

Clinical Potential of Induced Pluripotent Stem Cells

  • Chapter
  • First Online:

  • 465 Accesses

Part of the book series: Current Human Cell Research and Applications ((CHCRA))

Abstract

The ability to reprogram cells into induced pluripotent stem cells (iPSCs) has given a new perspective on cellular identity and cellular development. Since the original report of iPSCs, the range of methods and species in which iPSCs have been achieved demonstrates a universality of the pluripotency network and its maintenance. From a clinical perspective, iPSCs provide a new human cell model to study disease and innovate therapies. The reprogramming of patient cells provides a unique human cell model to investigate pathogenesis. iPSCs have especially strong appeal for the study of rare diseases or diseases that are normally diagnosed at late stage. Experimental therapies and drugs based on iPSC research are now at clinical stage. Additionally, drug repositioning using iPSC models has attracted heavy investment from industry. Despite their potential, iPSCs have inconsistent epigenetics with embryonic cells, which has retarded research on some cell lineages and related diseases. Regardless, there is anticipation that a large number of diseases will be treatable using iPSC-based products in the next decade.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Gurdon JB. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol. 1962;10:622–40.

    CAS  PubMed  Google Scholar 

  2. Takahashi K, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131:861–72. https://doi.org/10.1016/j.cell.2007.11.019.

    Article  CAS  PubMed  Google Scholar 

  3. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–76. https://doi.org/10.1016/j.cell.2006.07.024.

    Article  CAS  PubMed  Google Scholar 

  4. Yu J, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917–20. https://doi.org/10.1126/science.1151526.

    Article  CAS  PubMed  Google Scholar 

  5. Silva M, et al. Generating iPSCs: translating cell reprogramming science into scalable and robust biomanufacturing strategies. Cell Stem Cell. 2015;16:13–7. https://doi.org/10.1016/j.stem.2014.12.013.

    Article  CAS  PubMed  Google Scholar 

  6. Ogorevc J, Orehek S, Dovc P. Cellular reprogramming in farm animals: an overview of iPSC generation in the mammalian farm animal species. J Anim Sci Biotechnol. 2016;7:10. https://doi.org/10.1186/s40104-016-0070-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Polo JM, et al. Cell type of origin influences the molecular and functional properties of mouse induced pluripotent stem cells. Nat Biotechnol. 2010;28:848–55. https://doi.org/10.1038/nbt.1667.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Dimos JT, et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science. 2008;321:1218–21. https://doi.org/10.1126/science.1158799.

    Article  CAS  PubMed  Google Scholar 

  9. Ebert AD, et al. Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature. 2009;457:277–80. https://doi.org/10.1038/nature07677.

    Article  CAS  PubMed  Google Scholar 

  10. Lee G, et al. Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature. 2009;461:402–6. https://doi.org/10.1038/nature08320.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Li HL, Gee P, Ishida K, Hotta A. Efficient genomic correction methods in human iPS cells using CRISPR-Cas9 system. Methods. 2016;101:27–35. https://doi.org/10.1016/j.ymeth.2015.10.015.

    Article  CAS  PubMed  Google Scholar 

  12. Griesi-Oliveira K, et al. Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons. Mol Psychiatry. 2015;20:1350–65. https://doi.org/10.1038/mp.2014.141.

    Article  CAS  PubMed  Google Scholar 

  13. Marchetto MC, et al. Altered proliferation and networks in neural cells derived from idiopathic autistic individuals. Mol Psychiatry. 2017;22:820–35. https://doi.org/10.1038/mp.2016.95.

    Article  CAS  PubMed  Google Scholar 

  14. Haidet-Phillips AM, et al. Astrocytes from familial and sporadic ALS patients are toxic to motor neurons. Nat Biotechnol. 2011;29:824–8. https://doi.org/10.1038/nbt.1957.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Quadrato G, Brown J, Arlotta P. The promises and challenges of human brain organoids as models of neuropsychiatric disease. Nat Med. 2016;22:1220–8. https://doi.org/10.1038/nm.4214.

    Article  CAS  PubMed  Google Scholar 

  16. Trounson A, DeWitt ND. Pluripotent stem cells progressing to the clinic. Nat Rev Mol Cell Biol. 2016;17:194–200. https://doi.org/10.1038/nrm.2016.10.

    Article  CAS  PubMed  Google Scholar 

  17. Mandai M, et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. N Engl J Med. 2017;376:1038–46. https://doi.org/10.1056/NEJMoa1608368.

    Article  CAS  PubMed  Google Scholar 

  18. Garcia JM, et al. Stem cell therapy for retinal diseases. World J Stem Cells. 2015;7:160–4. https://doi.org/10.4252/wjsc.v7.i1.160.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Daley G, Polar Q. Extremes in the clinical use of stem cells. N Engl J Med. 2017;376:1075–7. https://doi.org/10.1056/NEJMe1701379.

    Article  PubMed  Google Scholar 

  20. Karagiannis P, Eto K. Ten years of induced pluripotency: from basic mechanisms to therapeutic applications. Development. 2016;143:2039–43. https://doi.org/10.1242/dev.138172.

    Article  CAS  PubMed  Google Scholar 

  21. Morizane A, et al. MHC matching improves engraftment of iPSC-derived neurons in non-human primates. Nat Commun. 2017;8:385. https://doi.org/10.1038/s41467-017-00926-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Shiba Y, et al. Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts. Nature. 2016;538:388–91. https://doi.org/10.1038/nature19815.

    Article  CAS  PubMed  Google Scholar 

  23. Zhao T, et al. Humanized mice reveal differential immunogenicity of cells derived from autologous induced pluripotent stem cells. Cell Stem Cell. 2015;17:353–9. https://doi.org/10.1016/j.stem.2015.07.021.

    Article  CAS  PubMed  Google Scholar 

  24. Gourraud PA, Gilson L, Girard M, Peschanski M. The role of human leukocyte antigen matching in the development of multiethnic “haplobank” of induced pluripotent stem cell lines. Stem Cells. 2012;30:180–6. https://doi.org/10.1002/stem.772.

    Article  CAS  PubMed  Google Scholar 

  25. Saito MK, Matsunaga A, Takasu N, Yamanaka S. In: Ilic D, editor. Stem cell banking. New York: Springer; 2014. p. 67–76.

    Chapter  Google Scholar 

  26. Azuma K, Yamanaka S. Recent policies that support clinical application of induced pluripotent stem cell-based regenerative therapies. Regen Ther. 2016;4:36–47.

    Article  Google Scholar 

  27. Nishimura T, et al. Generation of rejuvenated antigen-specific T cells by reprogramming to pluripotency and redifferentiation. Cell Stem Cell. 2013;12:114–26. https://doi.org/10.1016/j.stem.2012.11.002.

    Article  CAS  PubMed  Google Scholar 

  28. Vizcardo R, et al. Regeneration of human tumor antigen-specific T cells from iPSCs derived from mature CD8(+) T cells. Cell Stem Cell. 2013;12:31–6. https://doi.org/10.1016/j.stem.2012.12.006.

    Article  CAS  PubMed  Google Scholar 

  29. Maude SL, et al. The effect of pembrolizumab in combination with CD19-targeted chimeric antigen receptor (CAR) T cells in relapsed acute lymphoblastic leukemia (ALL). J Clin Oncol. 2017;35:103. https://doi.org/10.1200/JCO.2017.35.15_suppl.103.

    Article  Google Scholar 

  30. Kitayama S, et al. Cellular adjuvant properties, direct cytotoxicity of re-differentiated Valpha24 invariant NKT-like cells from human induced pluripotent stem cells. Stem Cell Reports. 2016;6:213–27. https://doi.org/10.1016/j.stemcr.2016.01.005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Sugimoto N, Eto K. Platelet production from induced pluripotent stem cells. J Thromb Haemost. 2017;15:1717–27. https://doi.org/10.1111/jth.13736.

    Article  CAS  PubMed  Google Scholar 

  32. Nakamura S, et al. Expandable megakaryocyte cell lines enable clinically applicable generation of platelets from human induced pluripotent stem cells. Cell Stem Cell. 2014;14:535–48. https://doi.org/10.1016/j.stem.2014.01.011.

    Article  CAS  PubMed  Google Scholar 

  33. Thon JN, Dykstra BJ, Beaulieu LM. Platelet bioreactor: accelerated evolution of design and manufacture. Platelets. 2017;28:472–7. https://doi.org/10.1080/09537104.2016.1265922.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bezard E, et al. Relationship between the appearance of symptoms and the level of nigrostriatal degeneration in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of Parkinson's disease. J Neurosci. 2001;21:6853–61.

    Article  CAS  Google Scholar 

  35. Avior Y, Sagi I, Benvenisty N. Pluripotent stem cells in disease modelling and drug discovery. Nat Rev Mol Cell Biol. 2016;17:170–82. https://doi.org/10.1038/nrm.2015.27.

    Article  CAS  PubMed  Google Scholar 

  36. Nosengo N. New tricks for old drugs. Nature. 2016;534:314–6.

    Article  Google Scholar 

  37. McNeish J, Gardner JP, Wainger BJ, Woolf CJ, Eggan K. From dish to bedside: lessons learned while translating findings from a stem cell model of disease to a clinical trial. Cell Stem Cell. 2015;17:8–10. https://doi.org/10.1016/j.stem.2015.06.013.

    Article  CAS  PubMed  Google Scholar 

  38. Imamura K, et al. The Src/c-Abl pathway is a potential therapeutic target in amyotrophic lateral sclerosis. Sci Transl Med. 2017;9:eaaf3962. https://doi.org/10.1126/scitranslmed.aaf3962.

    Article  PubMed  Google Scholar 

  39. Hino K, et al. Activin-A enhances mTOR signaling to promote aberrant chondrogenesis in fibrodysplasia ossificans progressiva. J Clin Invest. 2017;127(9):3339–52. https://doi.org/10.1172/JCI93521.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Yamashita A, et al. Statin treatment rescues FGFR3 skeletal dysplasia phenotypes. Nature. 2014;513:507–11. https://doi.org/10.1038/nature13775.

    Article  CAS  PubMed  Google Scholar 

  41. Moffat JG, Vincent F, Lee JA, Eder J, Prunotto M. Opportunities and challenges in phenotypic drug discovery: an industry perspective. Nat Rev Drug Discov. 2017;16:531–43. https://doi.org/10.1038/nrd.2017.111.

    Article  CAS  PubMed  Google Scholar 

  42. Karagiannis P, Onodera A, Yamanaka S. New models for therapeutic innovation from Japan. EBioMedicine. 2017;18:3–4. https://doi.org/10.1016/j.ebiom.2017.03.042.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Nozaki Y, et al. CSAHi study: validation of multi-electrode array systems (MEA60/2100) for prediction of drug-induced proarrhythmia using human iPS cell-derived cardiomyocytes-assessment of inter-facility and cells lot-to-lot-variability. Regul Toxicol Pharmacol. 2016;77:75–86. https://doi.org/10.1016/j.yrtph.2016.02.007.

    Article  CAS  PubMed  Google Scholar 

  44. Barbuti A, Benzoni P, Campostrini G, Dell’Era P. Human derived cardiomyocytes: a decade of knowledge after the discovery of induced pluripotent stem cells. Dev Dyn. 2016;245:1145–58. https://doi.org/10.1002/dvdy.24455.

    Article  CAS  PubMed  Google Scholar 

  45. Kawatou M, et al. Modelling Torsade de Pointes arrhythmias in vitro in 3D human iPS cell-engineered heart tissue. Nat Commun. 2017;8:1078. https://doi.org/10.1038/s41467-017-01125-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Yoshihara M, Hayashizaki Y, Murakawa Y. Genomic instability of iPSCs: challenges towards their clinical applications. Stem Cell Rev. 2017;13:7–16. https://doi.org/10.1007/s12015-016-9680-6.

    Article  CAS  PubMed  Google Scholar 

  47. Su RJ, et al. Few single nucleotide variations in exomes of human cord blood induced pluripotent stem cells. PLoS One. 2013;8:e59908. https://doi.org/10.1371/journal.pone.0059908.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kang E, et al. Age-related accumulation of somatic mitochondrial DNA mutations in adult-derived human iPSCs. Cell Stem Cell. 2016;18:625–36. https://doi.org/10.1016/j.stem.2016.02.005.

    Article  CAS  PubMed  Google Scholar 

  49. Rouhani F, et al. Genetic background drives transcriptional variation in human induced pluripotent stem cells. PLoS Genet. 2014;10:e1004432. https://doi.org/10.1371/journal.pgen.1004432.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zheng YL. Some ethical concerns about human induced pluripotent stem cells. Sci Eng Ethics. 2016;22:1277–84. https://doi.org/10.1007/s11948-015-9693-6.

    Article  PubMed  Google Scholar 

  51. Takashima Y, et al. Resetting transcription factor control circuitry toward ground-state pluripotency in human. Cell. 2014;158:1254–69. https://doi.org/10.1016/j.cell.2014.08.029.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Theunissen TW, et al. Systematic identification of culture conditions for induction and maintenance of naive human pluripotency. Cell Stem Cell. 2014;15:471–87. https://doi.org/10.1016/j.stem.2014.07.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Collier AJ, et al. Comprehensive cell surface protein profiling identifies specific markers of human naive and primed pluripotent states. Cell Stem Cell. 2017;20(6):874–890.e7. https://doi.org/10.1016/j.stem.2017.02.014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Choi J, et al. Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells. Nature. 2017;548:219–23. https://doi.org/10.1038/nature23274.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Yagi M, et al. Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation. Nature. 2017;548:224–7. https://doi.org/10.1038/nature23286.

    Article  CAS  PubMed  Google Scholar 

  56. Kajiwara M, et al. Donor-dependent variations in hepatic differentiation from human-induced pluripotent stem cells. Proc Natl Acad Sci U S A. 2012;109:12538–43. https://doi.org/10.1073/pnas.1209979109.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Kim K, et al. Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells. Nat Biotechnol. 2011;29:1117–9. https://doi.org/10.1038/nbt.2052.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH. Viable offspring derived from fetal and adult mammalian cells. Nature. 1997;385:810–3. https://doi.org/10.1038/385810a0.

    Article  CAS  PubMed  Google Scholar 

  59. Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature. 1981;292:154–6.

    Article  CAS  Google Scholar 

  60. Thomson JA, et al. Embryonic stem cell lines derived from human blastocysts. Science. 1998;282:1145–7.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

I thank Masaya Todani, Center for iPS Cell Research and Application (CiRA), Kyoto University (Japan), for the figure illustration.

Author information

Authors and Affiliations

  1. Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan

    Peter Karagiannis

Authors
  1. Peter Karagiannis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Karagiannis .

Editor information

Editors and Affiliations

  1. CiRA, Kyoto University, Kyoto, Japan

    Haruhisa Inoue

  2. Cell Engineering Division, RIKEN BioResource Research Center, Tsukuba-shi Ibaraki, Japan

    Yukio Nakamura

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Karagiannis, P. (2019). Clinical Potential of Induced Pluripotent Stem Cells. In: Inoue, H., Nakamura, Y. (eds) Medical Applications of iPS Cells . Current Human Cell Research and Applications. Springer, Singapore. https://doi.org/10.1007/978-981-13-3672-0_1

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-3672-0_1

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-3671-3

  • Online ISBN: 978-981-13-3672-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation