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Volumn 27, Issue 2, 2013, Pages 89-96

Uncertain translation, uncertain benefit and uncertain risk: Ethical challenges facing first-in-human trials of induced pluripotent stem (ips) cells

Author keywords

First in human trials; Parkinson's disease; Research ethics; Risk; Stem cells

Indexed keywords

ARTICLE; ETHICS; HUMAN; HUMAN EXPERIMENT; INFORMED CONSENT; PARKINSON DISEASE; PATIENT SELECTION; PLURIPOTENT STEM CELL; RISK ASSESSMENT; RISK MANAGEMENT; STEM CELL TRANSPLANTATION; TRANSLATIONAL RESEARCH; TRANSPLANTATION; UNCERTAINTY;

EID: 84872489192     PISSN: 02699702     EISSN: 14678519     Source Type: Journal    
DOI: 10.1111/j.1467-8519.2011.01896.x     Document Type: Article
Times cited : (24)

References (45)
  • 1
    • 84872487886 scopus 로고    scopus 로고
    • National Institutes of Health, US Department of Health and Human Services. 2009. The National Institutes of Health resource for stem cell research: Stem Cell Basics. Bethesda, MD. Available at
    • National Institutes of Health, US Department of Health and Human Services. 2009. The National Institutes of Health resource for stem cell research: Stem Cell Basics. Bethesda, MD. Available at: http://stemcells.nih.gov/info/basics/defaultpage2010
    • (2010)
  • 2
    • 59549103327 scopus 로고    scopus 로고
    • Ethical Issues of the Research on Human Embryonic Stem Cells
    • Y. Hotta. Ethical Issues of the Research on Human Embryonic Stem Cells. J Int Bioethique 2008; 19: 77-85.
    • (2008) J Int Bioethique , vol.19 , pp. 77-85
    • Hotta, Y.1
  • 3
    • 0029967424 scopus 로고    scopus 로고
    • Sheep Cloned by Nuclear Transfer from a Cultured Cell Line
    • K.H. Campbell et al. Sheep Cloned by Nuclear Transfer from a Cultured Cell Line. Nature 1996; 380: 64-66.
    • (1996) Nature , vol.380 , pp. 64-66
    • Campbell, K.H.1
  • 4
    • 34447098931 scopus 로고    scopus 로고
    • ESHRE Task Force on Ethics and Law 12: Oocyte Donation for Non-reproductive Purposes
    • G. Pennings et al. ESHRE Task Force on Ethics and Law 12: Oocyte Donation for Non-reproductive Purposes. Hum Reprod 2007; 22: 1210-1213.
    • (2007) Hum Reprod , vol.22 , pp. 1210-1213
    • Pennings, G.1
  • 5
    • 36248966518 scopus 로고    scopus 로고
    • Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
    • K. Takahashi et al. Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors. Cell 2007; 131: 861-872.
    • (2007) Cell , vol.131 , pp. 861-872
    • Takahashi, K.1
  • 6
    • 48749109823 scopus 로고    scopus 로고
    • Pluripotent Stem Cell Lines
    • J. Yu & J.A. Thomson. Pluripotent Stem Cell Lines. Genes Dev 2008: 22: 1987-1997.
    • (2008) Genes Dev , vol.22 , pp. 1987-1997
    • Yu, J.1    Thomson, J.A.2
  • 7
    • 67649222358 scopus 로고    scopus 로고
    • Induced Pluripotent Stem Cells and Embryonic Stem Cells are Distinguished by Gene Expression Signatures
    • M.H. Chin et al. Induced Pluripotent Stem Cells and Embryonic Stem Cells are Distinguished by Gene Expression Signatures. Cell Stem Cell 2009; 5: 111-123.
    • (2009) Cell Stem Cell , vol.5 , pp. 111-123
    • Chin, M.H.1
  • 8
    • 77950995392 scopus 로고    scopus 로고
    • Hemangioblast Derivatives from Human Induced Pluripotent Stem Cells Exhibit Limited Expansion and Early Senescence
    • Q. Feng et al. Hemangioblast Derivatives from Human Induced Pluripotent Stem Cells Exhibit Limited Expansion and Early Senescence. Stem Cells 2010; 28: 704-712.
    • (2010) Stem Cells , vol.28 , pp. 704-712
    • Feng, Q.1
  • 9
    • 74949133926 scopus 로고    scopus 로고
    • Progress Toward the Clinical Application of Patient-specific Pluripotent Stem Cells
    • E. Kiskinis & K. Eggan. Progress Toward the Clinical Application of Patient-specific Pluripotent Stem Cells. J Clin Invest 2010; 120: 51-59.
    • (2010) J Clin Invest , vol.120 , pp. 51-59
    • Kiskinis, E.1    Eggan, K.2
  • 10
    • 67651204314 scopus 로고    scopus 로고
    • Ontological and Ethical Implications of Direct Nuclear Reprogramming: Response to Magill and Neaves
    • M.L. Condic, P. Lee & R.P. George. Ontological and Ethical Implications of Direct Nuclear Reprogramming: Response to Magill and Neaves. Kennedy Inst Ethics J 2009; 19: 33-40.
    • (2009) Kennedy Inst Ethics J , vol.19 , pp. 33-40
    • Condic, M.L.1    Lee, P.2    George, R.P.3
  • 11
    • 84872501524 scopus 로고    scopus 로고
    • ES Cells and iPS Cells: A Distinction with a Difference. Garrison, NY: The Hastings Center. Available at
    • F. Baylis. 2008. ES Cells and iPS Cells: A Distinction with a Difference. Garrison, NY: The Hastings Center. Available athttp://www.thehastingscenter.org/Bioethicsforum/Post.aspx?id=7302010
    • (2008)
    • Baylis, F.1
  • 12
    • 71149109708 scopus 로고    scopus 로고
    • IPS Cells: Mapping the Policy Issues
    • A. Zarzeczny et al. IPS Cells: Mapping the Policy Issues. Cell 2009; 139: 1032-1037.
    • (2009) Cell , vol.139 , pp. 1032-1037
    • Zarzeczny, A.1
  • 13
    • 36248933671 scopus 로고    scopus 로고
    • Cognitive Dysfunction and Dementia in Parkinson Disease
    • N. Caballol, M.J. Martí & E. Tolosa. Cognitive Dysfunction and Dementia in Parkinson Disease. Mov Disord 2007; 22: S358-S366.
    • (2007) Mov Disord , vol.22
    • Caballol, N.1    Martí, M.J.2    Tolosa, E.3
  • 15
    • 0033551330 scopus 로고    scopus 로고
    • Transient Acute Depression Induced by High-frequency Deep-brain Stimulation
    • B.P. Bejjani et al. Transient Acute Depression Induced by High-frequency Deep-brain Stimulation. N Engl J Med 1999; 340: 1476-1480.
    • (1999) N Engl J Med , pp. 1476-1480
    • Bejjani, B.P.1
  • 16
    • 42649130264 scopus 로고    scopus 로고
    • Neurons Derived from Reprogrammed Fibroblasts Functionally Integrate into the Fetal Brain and Improve Symptoms of Rats with Parkinson's Disease
    • M. Wernig et al. Neurons Derived from Reprogrammed Fibroblasts Functionally Integrate into the Fetal Brain and Improve Symptoms of Rats with Parkinson's Disease. Proc Natl Acad Sci U S A. 2008; 105: 5856-5861.
    • (2008) Proc Natl Acad Sci U S A. , vol.105 , pp. 5856-5861
    • Wernig, M.1
  • 17
    • 67449083632 scopus 로고    scopus 로고
    • Multitracer Assessment of Dopamine Function after Transplantation of Embryonic Stem Cell-derived Neural Stem Cells in a Primate Model of Parkinson's Disease
    • S. Muramatsu et al. Multitracer Assessment of Dopamine Function after Transplantation of Embryonic Stem Cell-derived Neural Stem Cells in a Primate Model of Parkinson's Disease. Synapse 2009; 63: 541-548.
    • (2009) Synapse , vol.63 , pp. 541-548
    • Muramatsu, S.1
  • 18
    • 84872490618 scopus 로고    scopus 로고
    • World Medical Association (WMA). 2008. Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subjects. Ferney-Voltaire, France: WMA
    • World Medical Association (WMA). 2008. Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subjects. Ferney-Voltaire, France: WMA. Available at: http://www.wma.net/en/30publications/10policies/b3/index.html2010.
    • (2008)
  • 19
    • 84872493028 scopus 로고    scopus 로고
    • International Society for Stem Cell Research (ISSCR). 2008. Guidelines for the Clinical Translation of Stem Cells. Deerfield, IL: ISSCR. Available at:
    • International Society for Stem Cell Research (ISSCR). 2008. Guidelines for the Clinical Translation of Stem Cells. Deerfield, IL: ISSCR. Available at: http://www.isscr.org/clinical_trans/pdfs/ISSCRGLClinicalTrans.pdf2010
    • (2010)
  • 20
    • 61349126697 scopus 로고    scopus 로고
    • First-in-Human Trial Participants: Not a Vulnerable Population, but Vulnerable Nonetheless
    • R. Dresser. First-in-Human Trial Participants: Not a Vulnerable Population, but Vulnerable Nonetheless. J Law Med Ethics 2009; 37: 38-50.
    • (2009) J Law Med Ethics , vol.37 , pp. 38-50
    • Dresser, R.1
  • 21
    • 0035826089 scopus 로고    scopus 로고
    • Transplantation of Embryonic Dopamine Neurons for Severe Parkinson's Disease
    • C.R. Freed et al. Transplantation of Embryonic Dopamine Neurons for Severe Parkinson's Disease. N Engl J Med 2001; 344: 710-719.
    • (2001) N Engl J Med , vol.344 , pp. 710-719
    • Freed, C.R.1
  • 22
    • 34249880066 scopus 로고    scopus 로고
    • Generation of Germline-Competent Induced Pluripotent Stem Cells
    • K. Okita, T. Ichisaka & S. Yamanaka. Generation of Germline-Competent Induced Pluripotent Stem Cells. Nature 2007; 448: 313-317.
    • (2007) Nature , vol.448 , pp. 313-317
    • Okita, K.1    Ichisaka, T.2    Yamanaka, S.3
  • 23
    • 0242409776 scopus 로고    scopus 로고
    • Safety Issues in Cell-based Intervention Trials
    • L. Dawson et al. Safety Issues in Cell-based Intervention Trials. Fertil Steril 2003; 80: 1077-1085.
    • (2003) Fertil Steril , vol.80 , pp. 1077-1085
    • Dawson, L.1
  • 24
    • 0036319775 scopus 로고    scopus 로고
    • Suicide Gene Transduction Sensitizes Murine Embryonic and Human Mesenchymal Stem Cells to Ablation on Demand - a Fail-safe Protection against Cellular Misbehavior
    • M.U. Fareed & F.L. Moolten. Suicide Gene Transduction Sensitizes Murine Embryonic and Human Mesenchymal Stem Cells to Ablation on Demand - a Fail-safe Protection against Cellular Misbehavior. Gene Ther 2002; 9: 955-962.
    • (2002) Gene Ther , vol.9 , pp. 955-962
    • Fareed, M.U.1    Moolten, F.L.2
  • 25
    • 71549171119 scopus 로고    scopus 로고
    • Role of MEF Feeder Cells in Direct Reprogramming of Mousetail-tip Fibroblasts
    • M. Chen et al. Role of MEF Feeder Cells in Direct Reprogramming of Mousetail-tip Fibroblasts. Cell Biol Int 2009; 33: 1268-1273.
    • (2009) Cell Biol Int , vol.33 , pp. 1268-1273
    • Chen, M.1
  • 26
    • 77953966510 scopus 로고    scopus 로고
    • Human Induced Pluripotent Stem Cells on Autologous Feeders
    • K. Takahashi et al. Human Induced Pluripotent Stem Cells on Autologous Feeders. PLoS One 2009; 4: e8067.
    • (2009) PLoS One , vol.4
    • Takahashi, K.1
  • 27
    • 46649111324 scopus 로고    scopus 로고
    • Animal Models of Parkinson's Disease and L-dopa Induced Dyskinesia: How Close Are We to the Clinic?
    • E. Lane & S. Dunnett. Animal Models of Parkinson's Disease and L-dopa Induced Dyskinesia: How Close Are We to the Clinic? Psychopharmacology (Berl) 2008; 199: 303-312.
    • (2008) Psychopharmacology (Berl) , vol.199 , pp. 303-312
    • Lane, E.1    Dunnett, S.2
  • 28
    • 0036159538 scopus 로고    scopus 로고
    • Brasofensine Treatment for Parkinson's Disease in Combination with Levodopa/carbidopa
    • E.J. Frackiewicz et al. Brasofensine Treatment for Parkinson's Disease in Combination with Levodopa/carbidopa. Ann Pharmacother 2002; 36: 225-230.
    • (2002) Ann Pharmacother , vol.36 , pp. 225-230
    • Frackiewicz, E.J.1
  • 29
    • 77952850583 scopus 로고    scopus 로고
    • Gene transfer and the ethics of first-in-human research: lost in translation
    • Cambridge, UK: Cambridge University Press.
    • J. Kimmelman. 2010. Gene transfer and the ethics of first-in-human research: lost in translation. Cambridge, UK: Cambridge University Press.
    • (2010)
    • Kimmelman, J.1
  • 30
    • 33846630040 scopus 로고    scopus 로고
    • Humanized Mice in Translational Biomedical Research
    • L.D. Shultz, F. Ishikawa & D.L. Greiner. Humanized Mice in Translational Biomedical Research. Nat Rev Immunol 2007; 7: 118-130.
    • (2007) Nat Rev Immunol , vol.7 , pp. 118-130
    • Shultz, L.D.1    Ishikawa, F.2    Greiner, D.L.3
  • 31
    • 0029677420 scopus 로고    scopus 로고
    • The Origin of Speciesism
    • H. LaFollette & N. Shanks. The Origin of Speciesism. Philosophy 1996; 71: 41-61
    • (1996) Philosophy , vol.71 , pp. 41-61
    • LaFollette, H.1    Shanks, N.2
  • 32
    • 84872488706 scopus 로고
    • Created from Animals. Oxford: Oxford University Press: 220. According to the theory of 'causal functional asymmetry', the logical dilemma arises where the assertion that humans and non-human animals share significant biological mechanisms, such that experiments on the latter can shed light on the former, seems to be at odds with the claim that they are, at the same time, substantially different as far as moral capacity is concerned. As Rachels succinctly puts it, 'If the animal subjects are not sufficiently like us to produce a model, then the experiments may be pointless. but if the animals are enough like us to provide a model, it may be impossible to justify treating them in ways we would not treat humans
    • J. Rachels. 1990. Created from Animals. Oxford: Oxford University Press: 220. According to the theory of 'causal functional asymmetry', the logical dilemma arises where the assertion that humans and non-human animals share significant biological mechanisms, such that experiments on the latter can shed light on the former, seems to be at odds with the claim that they are, at the same time, substantially different as far as moral capacity is concerned. As Rachels succinctly puts it, 'If the animal subjects are not sufficiently like us to produce a model, then the experiments may be pointless. but if the animals are enough like us to provide a model, it may be impossible to justify treating them in ways we would not treat humans
    • (1990)
    • Rachels, J.1
  • 33
    • 77958117129 scopus 로고    scopus 로고
    • Editorial. Reduce, refine, replace. Nature Immunol
    • Editorial. Reduce, refine, replace. Nature Immunol 2010; 11: 971.
    • (2010) , vol.11 , pp. 971
  • 34
    • 33846476725 scopus 로고    scopus 로고
    • Elucidating the Pathophysiology of Delirium and the Interrelationship of Delirium and Dementia
    • S.K. Inouye & L. Ferrucci. Elucidating the Pathophysiology of Delirium and the Interrelationship of Delirium and Dementia. J Gerontol A Biol Sci Med Sci 2006; 61: 1277-1280.
    • (2006) J Gerontol A Biol Sci Med Sci , vol.61 , pp. 1277-1280
    • Inouye, S.K.1    Ferrucci, L.2
  • 35
    • 0016823810 scopus 로고
    • Mini-mental state. A Practical Method for Grading the Cognitive State of Patients for the Clinician
    • M.F. Folstein, S.E. Folstein & P.R. McHugh. Mini-mental state. A Practical Method for Grading the Cognitive State of Patients for the Clinician. J Psychiatr Res 1975; 12: 189-198.
    • (1975) J Psychiatr Res , vol.12 , pp. 189-198
    • Folstein, M.F.1    Folstein, S.E.2    McHugh, P.R.3
  • 37
    • 0032852373 scopus 로고    scopus 로고
    • Competence of Depressed Patients for Consent to Research
    • P.S. Appelbaum et al. Competence of Depressed Patients for Consent to Research. Am J Psychiatry 1999; 156: 1380-1384.
    • (1999) Am J Psychiatry , vol.156 , pp. 1380-1384
    • Appelbaum, P.S.1
  • 38
    • 0036789018 scopus 로고    scopus 로고
    • Utility and Limits of the Mini Mental State Examination in Evaluating Consent Capacity in Alzheimer's disease
    • S.Y. Kim & E.D. Caine. Utility and Limits of the Mini Mental State Examination in Evaluating Consent Capacity in Alzheimer's disease. Psychiatr Serv 2002; 53: 1322-1324.
    • (2002) Psychiatr Serv , vol.53 , pp. 1322-1324
    • Kim, S.Y.1    Caine, E.D.2
  • 39
    • 39749104221 scopus 로고    scopus 로고
    • Predictors of Providing Informed Consent or Assent for Research Participation in Assisted Living Residents
    • B.S. Black et al. Predictors of Providing Informed Consent or Assent for Research Participation in Assisted Living Residents. Am J Geriatr Psychiatry 2008; 16: 83-91
    • (2008) Am J Geriatr Psychiatry , vol.16 , pp. 83-91
    • Black, B.S.1
  • 40
    • 50549094908 scopus 로고    scopus 로고
    • Cell-based Interventions for Neurologic Conditions: Ethical Challenges for Early Human Trials
    • D.J. Mathews et al. Cell-based Interventions for Neurologic Conditions: Ethical Challenges for Early Human Trials. Neurology 2008; 71: 288-293.
    • (2008) Neurology , vol.71 , pp. 288-293
    • Mathews, D.J.1
  • 41
    • 77955330160 scopus 로고    scopus 로고
    • Dementia, Goals of Care, and Personhood: a Study of Surrogate Decision Makers' Beliefs and Values
    • L.C. Kaldjian et al. Dementia, Goals of Care, and Personhood: a Study of Surrogate Decision Makers' Beliefs and Values. Am J Hosp Palliat Care 2010; 27: 387-397.
    • (2010) Am J Hosp Palliat Care , vol.27 , pp. 387-397
    • Kaldjian, L.C.1
  • 42
    • 84872486332 scopus 로고    scopus 로고
    • Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Social Sciences and Humanities Research Council of Canada. 1998. Tri-council policy statement: Ethical conduct for research involving humans. Ottawa, ON. Available at:
    • Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Social Sciences and Humanities Research Council of Canada. 1998. Tri-council policy statement: Ethical conduct for research involving humans. Ottawa, ON. Available at:http://pre.ethics.gc.ca/eng/policy-politique/tcps-eptc2010
    • (2010)
  • 43
    • 74749088366 scopus 로고    scopus 로고
    • A Changing Landscape for Advance Directives in Dementia Research
    • R. Pierce. A Changing Landscape for Advance Directives in Dementia Research. Soc Sci Med 2010; 70: 623-630.
    • (2010) Soc Sci Med , vol.70 , pp. 623-630
    • Pierce, R.1
  • 44
    • 18444374124 scopus 로고    scopus 로고
    • For a more detailed analysis of the phenomenon of therapeutic misconception which is widely observed in clinical research, see: N.M. King et al. Consent Forms and the Therapeutic Misconception: the Example of Gene Transfer Research
    • For a more detailed analysis of the phenomenon of therapeutic misconception which is widely observed in clinical research, see: N.M. King et al. Consent Forms and the Therapeutic Misconception: the Example of Gene Transfer Research. 2005; 27: 1-8
    • (2005) , vol.27 , pp. 1-8
  • 45
    • 74049154451 scopus 로고    scopus 로고
    • Stem Cell Research Policy and iPS Cells
    • T. Caulfield et al. Stem Cell Research Policy and iPS Cells. Nat Methods 2010; 7: 28-33.
    • (2010) Nat Methods , vol.7 , pp. 28-33
    • Caulfield, T.1


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