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Stem Cell Reviews and Reports

, Volume 10, Issue 2, pp 145–150 | Cite as

Great Expectations: Autism Spectrum Disorder and Induced Pluripotent Stem Cell Technologies

  • Emily Yang LiuEmail author
  • Christopher Thomas Scott
Article

Abstract

New applications of iPSC technology to research on complex idiopathic conditions raise several important ethical and social considerations for potential research participants and their families. In this short review, we examine these issues through the lens of emerging research on autism spectrum disorder (ASD). We begin by describing the current state of iPSC technology in research on ASD. Then we discuss how the social history of and current controversies in autism research combined with the emergence of autism-specific iPSC biobanks indicate an urgent need for researchers to clearly communicate the limitations and possibilities of iPSC research to ensure research participants have the ability to provide fully informed, voluntary consent. We conclude by offering recommendations to bolster informed consent for research involving iPSC biobanks, both in the specific context of ASD and more broadly.

Keywords

Induced pluripotent stem cells Human embryonic stem cells Autism spectrum disorder Biobanks Ethics Informed consent Patient autonomy 

Notes

Acknowledgments

EYL is supported by the Stanford Center for Biomedical Ethics and NIH grant P50 HG003389 (Center for Integrating Ethics and Genetics Research). CTS is supported by the Stanford Center for Biomedical Ethics and the Stanford Institute for Stem Cell Biology and Regenerative Medicine. The authors thank Lauren C. Milner for her contribution to the conceptual phase of this work and Vittorio Sebastiano for his valuable assistance with the manuscript.

Conflict of Interest

The authors declare no potential conflicts of interest.

References

  1. 1.
    Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., et al. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131(5), 861–872.PubMedCrossRefGoogle Scholar
  2. 2.
    Jang, J., Yoo, J. E., Lee, J. A., Lee, D. R., Kim, J. Y., Huh, Y. J., et al. (2012). Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery. Experimental and Molecular Medicine, 44(3), 202–213.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Marchetto, M. C., Brennand, K. J., Boyer, L. F., & Gage, F. H. (2011). Induced pluripotent stem cells (iPSCs) and neurological disease modeling: progress and promises. Human Molecular Genetics, 20(2), R109–R115.PubMedCrossRefGoogle Scholar
  4. 4.
    American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington: American Psychiatric Publishing.Google Scholar
  5. 5.
    Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators. (2012). Prevalence of autism spectrum disorders—autism and developmental disabilities monitoring network, 14 sites, United States, 2008. Resource document. Centers for Disease Control and Prevention. http://www.cdc.gov/mmwr/preview/mmwrhtml/ss6103a1.htm?s_cid=ss6103a1_w. Accessed 15 July 2013.
  6. 6.
    Interagency Autism Coordinating Committee. (2012). 2010 Autism spectrum disorder research portfolio analysis report. http://iacc.hhs.gov/portfolio-analysis/2010/index.shtml. Accessed 5 June 2013.
  7. 7.
    Wu, S. M., & Hochedlinger, K. (2011). Harnessing the potential of induced pluripotent stem cells for regenerative medicine. Nature Cell Biology, 13(5), 497–505.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Dimos, J. T., Griswold-Prenner, I., Grskovic, M., Irion, S., Johnson, C., & Vaisberg, E. (2011). Induced pluripotent stem cells as human disease models. Annual Reports in Medicinal Chemistry, 46, 369–383.CrossRefGoogle Scholar
  9. 9.
    Grskovic, M., Javaherian, A., Strulovici, B., & Daley, G. Q. (2011). Induced pluripotent stem cells—opportunities for disease modeling and drug discovery. Nature Reviews Drug Discovery, 10(12), 915–929.PubMedGoogle Scholar
  10. 10.
    Ebert, A. D., Yu, J., Rose, F. F., Jr., Mattis, V. B., Lorson, C. L., Thomson, J. A., et al. (2009). Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature, 457(7227), 277–280.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Sinnecker, D., Dirschinger, R. J., Goedel, A., Moretti, A., Lipp, P., & Laugwitz, K. L. (2012). Induced pluripotent stem cells in cardiovascular research. Reviews of Physiology, Biochemistry and Pharmacology, 163, 1–26.PubMedGoogle Scholar
  12. 12.
    Bruck, T., & Benvenisty, N. (2011). Meta-analysis of the heterogeneity of X chromosome inactivation in human pluripotent stem cells. Stem Cell Research, 6(2), 187–193.PubMedCrossRefGoogle Scholar
  13. 13.
    Gore, A., Li, Z., Fung, H. L., Young, J. E., Agarwal, S., Antosiewicz-Bourget, J., et al. (2011). Somatic coding mutations in human induced pluripotent stem cells. Nature, 471(7336), 63–67.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Hussein, S. M., Batada, N. N., Vuoristo, S., Ching, R. W., Autio, R., Närvä, E., et al. (2011). Copy number variation and selection during reprogramming to pluripotency. Nature, 471(7336), 58–62.PubMedCrossRefGoogle Scholar
  15. 15.
    Lister, R., Pelizzola, M., Kida, Y. S., Hawkins, R. D., Nery, J. R., Hon, G., et al. (2011). Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells. Nature, 471(7336), 68–73.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Mayshar, Y., Ben-David, U., Lavon, N., Biancotti, J. C., Yakir, B., Clark, A. T., et al. (2010). Identification and classification of chromosomal aberrations in human induced pluripotent stem cells. Cell Stem Cell, 7(4), 521–531.PubMedCrossRefGoogle Scholar
  17. 17.
    Pick, M., Stelzer, Y., Bar-Nur, O., Mayshar, Y., Eden, A., & Benvenisty, N. (2009). Clone- and gene-specific aberrations of parental imprinting in human induced pluripotent stem cells. Stem Cells, 27(11), 2686–2690.PubMedCrossRefGoogle Scholar
  18. 18.
    National Institutes of Health. (2012). Stem cells and diseases. http://stemcells.nih.gov/info//pages/health.aspx. Accessed 14 October 2013.
  19. 19.
    Joung, J. K., & Sander, J. D. (2013). TALENs: a widely applicable technology for targeted genome editing. Nature Reviews Molecular Cell Biology, 14(1), 49–55.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    DeRosa, B. A., Van Baaren, J. M., Dubey, G. K., Lee, J. M., Cuccaro, M. L., Vance, J. M., et al. (2012). Derivation of autism spectrum disorder-specific induced pluripotent stem cells from peripheral blood mononuclear cells. Neuroscience Letters, 516(1), 9–14.PubMedCrossRefGoogle Scholar
  21. 21.
    Kim, K. Y., Jung, Y. W., Sullivan, G. J., Chung, L., & Park, I. H. (2012). Cellular reprogramming: a novel tool for investigating autism spectrum disorders. Trends in Molecular Medicine, 18(8), 463–471.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Marchetto, M. C., Winner, B., & Gage, F. H. (2010). Pluripotent stem cells in neurodegenerative and neurodevelopmental diseases. Human Molecular Genetics, 19(1), R71–R76.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Farra, N., Zhang, W. B., Pasceri, P., Eubanks, J. H., Salter, M. W., & Ellis, J. (2012). Rett syndrome induced pluripotent stem cell-derived neurons reveal novel neurophysiological alterations. Molecular Psychiatry, 17(12), 1261–1271.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Pasca, S. P., Portmann, T., Voineagu, I., Yazawa, M., Shcheglovitov, O., Pasca, A. M., et al. (2012). Using iPS cell-derived neurons to uncover cellular phenotypes associated with Timothy Syndrome. Nature Medicine, 17(12), 1657–1662.CrossRefGoogle Scholar
  25. 25.
    National Human Genome Institute. (2012). Learning about autism. http://www.genome.gov/25522099. Accessed 14 October 2013.
  26. 26.
    Urbach, A., Bar-Nur, O., Daley, G. Q., & Benvenisty, N. (2010). Differential modeling of Fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell, 6(5), 407–411.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Trounson, A., Shepard, K. A., & DeWitt, N. D. (2012). Human disease modeling with induced pluripotent stem cells. Current Opinion in Genetics and Development, 22(5), 509–516.PubMedCrossRefGoogle Scholar
  28. 28.
    Zarzeczny, A. T., Scott, C. T., Hyun, I., Bennett, J., Chandler, J., Chargé, S., et al. (2009). iPS cells: mapping the policy issues. Cell, 139(6), 1032–1037.PubMedCrossRefGoogle Scholar
  29. 29.
    NIH RePORT. Project information: 5R01HD059967-03. http://projectreporter.nih.gov/project_info_description.cfm?projectnumber=5R01HD059967-03. Accessed 29 September 2013.
  30. 30.
    U.S. Department of Health and Human Services. (2009). 45 CFR 46. http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html. Accessed 12 September 2013.
  31. 31.
    Wolf, S. M., Lawrenz, F. P., Nelson, C. A., Kahn, J. P., Cho, M. K., Clayton, E. W., et al. (2008). Managing incidental findings in human subjects research: analysis and recommendations. Journal of Law and Medical Ethics, 32(2), 219–248.CrossRefGoogle Scholar
  32. 32.
    Knoppers, B. M., & Isasi, R. (2010). Stem cell banking: between traceability and identifiability. Genome Medicine, 2(10), 73.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Resnik, D. B. (2009). Re-consenting human subjects: ethical, legal, and practical issues. Journal of Medical Ethics, 35(11), 656–657.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Eriksson, S., & Helgesson, G. (2005). Potential harms, anonymization, and the right to withdraw consent to biobank research. European Journal of Humanities and Genetics, 13(9), 1071–1076.CrossRefGoogle Scholar
  35. 35.
    Connor, S. (2013). Breakthrough with stem cells could “end need for transplants.” The Independent. http://wwww.independent.co.ulk/news/science/breakthrough-with-stem-cells-could-end-need-for-transplants-8809955.html. Accessed 28 September 2013.
  36. 36.
    Gray, R. (2013). Stem cell study raises hopes that organs could be regenerated inside patients’ own bodies. Telegraph. http://www.telegraph.co.uk/science/10302341/Stem-cell-study-raises-hopes-that-organs-could-be-regenerated-inside-patients-own-bodies.html. Accessed 29 September 2013.
  37. 37.
    Innes, E. (2013). The pea-sized brains created from SKIN that could lead to cures for disorders such as schizophrenia and autism. Mail Online. http://www.dailymail.co.uk/sciencetech/article-2404537/Tiny-brains-created-SKIN-lead-cures-disorders-like-schizophrenia-autism.html. Accessed 29 September 2013.
  38. 38.
    Kiatpongsan, S., & Sipp, D. (2009). Monitoring and regulating offshore stem cell clinics. Science, 323(5921), 1564–1565.PubMedCrossRefGoogle Scholar
  39. 39.
    Murdoch, C. E., & Scott, C. T. (2010). Stem cell tourism and the power of hope. American Journal of Bioethics, 10(5), 16–23.PubMedCrossRefGoogle Scholar
  40. 40.
    Jensen, C. (2013). Animal stem cells help local boy with autism. NPG of Idaho. http://www.localnews8.com/news/Animal-stem-cells-help-local-boy-with-autism/-/308662/19642398/-/bavlmy/-/index.html. Accessed 29 September 2013.
  41. 41.
    Moral, C. V. (2013). Karen Davila resorts to stem-cell therapy for son’s autism. Inquirer Lifestyle. http://lifestyle.inquirer.net/90269/karen-davila-resorts-to-stem-cell-therapy-for-sons-autism. Accessed 29 September 2013.
  42. 42.
    Singer, E. (2003). Exploring the meaning of consent: participation in research and beliefs about risks and benefits. Journal of Official Statistics, 19(3), 273–285.Google Scholar
  43. 43.
    Singer, E. (2004). Risk, benefit, and informed consent in survey research. Survey Research, 25(2–3), 2–24.Google Scholar
  44. 44.
    Bagatell, N. (2010). From cure to community: transforming notions of autism. Ethos, 38(1), 33–55.CrossRefGoogle Scholar
  45. 45.
    Kapp, S. K., Gillespie-Lynch, K., Sherman, L. E., & Hutman, T. (2013). Deficit, difference, or both? Autism and neurodiversity. Developmental Psychology, 49(1), 59–71.PubMedCrossRefGoogle Scholar
  46. 46.
    Orsini, M. (2009). Contesting the autistic subject: Biological citizenship and the autism/autistic movement. In S. Murray & D. Holmes (Eds.), Critical interventions in the ethics of healthcare (pp. 115–130). Abingon, Oxon, GBR: Ashgate Publishing Group.Google Scholar
  47. 47.
    Kreiner, T., & Irion, S. (2013). Whole-genome analysis, stem cell research, and the future of biobanks. Cell Stem Cell, 12(5), 513–516.PubMedCrossRefGoogle Scholar
  48. 48.
    United Nations Educational, Scientific and Cultural Organization (UNESCO). Report of the International Bioethics Committee of UNESCO (IBC) on consent. (IBC, 2008). http://unesdoc.unesco.org/images/0017/001781/178124e.pdf. Accessed 29 September 2013.
  49. 49.
    Steinsbekk, K. S., Kare Myskja, B., & Solberg, B. (2013). Broad consent versus dynamic consent in biobank research: is passive participation an ethical problem? European Journal of Human Genetics, 21(9), 897–902.PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Scott, C. T., Caulfield, T., Borgelt, E., & Illes, J. (2012). Personal medicine—the new banking crisis. Nature Biotechnology, 30(2), 141–147.PubMedCrossRefGoogle Scholar
  51. 51.
    Isasi, R., Knoppers, B. M., & Lomax, G. (2011). Sustained interaction: the new normal for stem cell repositories? Regenerative Medicine, 6(6), 783–792.PubMedCrossRefGoogle Scholar
  52. 52.
    Cambon-Thomsen, A., Rial-Sebbag, E., & Knoppers, B. M. (2007). Trends in ethical and legal frameworks for the use of human biobanks. European Respiratory Journal, 30(2), 373–382.PubMedCrossRefGoogle Scholar
  53. 53.
    Clayton, E. W. (2005). Informed consent and biobanks. Journal of Law, Medicine, & Ethics, 33(1), 15–21.CrossRefGoogle Scholar
  54. 54.
    Secko, D. M., Preto, N., Niemeyer, S., & Burgess, M. M. (2009). Informed consent in biobank research: a deliberative approach to the debate. Social Science & Medicine, 68(4), 781–789.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Stanford University Center for Biomedical EthicsStanfordUSA
  2. 2.Stanford University Program on Stem Cells in SocietyStanfordUSA

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