Human tissues in a dish: The research and ethical implications of organoid technology

Science

Volumn 355, Issue 6322, 2017, Pages

  Bredenoord, Annelien L ^a   Clevers, Hans ^a   Knoblich, Juergen A ^b  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^b INSTITUTE OF MOLECULAR BIOTECHNOLOGY   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

CELLS AND CELL COMPONENTS; DISEASE INCIDENCE; EMBRYO; ETHICS; GENE TRANSFER; INNOVATION; MEDICINE; RESEARCH WORK;

ANIMAL EXPERIMENT; CLINICAL RESEARCH; CYTOPLASM; FETUS (ANATOMY); GENE EDITING; HUMAN; HUMAN EMBRYO; HUMAN TISSUE; MEDICAL RESEARCH; MEDICAL TECHNOLOGY; NONHUMAN; ORGAN TRANSPLANTATION; PERSONALIZED MEDICINE; PRIORITY JOURNAL; RESEARCH ETHICS; REVIEW; ANIMAL; CYTOLOGY; EMBRYO RESEARCH; ETHICS; FETAL RESEARCH; GROWTH, DEVELOPMENT AND AGING; STEM CELL RESEARCH; TISSUE CULTURE TECHNIQUE; TRANSPLANTATION;

ANIMALIA;

ANIMAL EXPERIMENTATION; ANIMALS; EMBRYO RESEARCH; FETAL RESEARCH; GENE EDITING; HUMANS; ORGANOIDS; PRECISION MEDICINE; STEM CELL RESEARCH; TISSUE CULTURE TECHNIQUES;

EID: 85010637378     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.aaf9414     Document Type: Review

References (64)

1. M. A. Lancaster, J. A. Knoblich, Organogenesis in a dish: Modeling development and disease using organoid technologies. Science 345, 1247125 (2014). doi: 10.1126/science.1247125; pmid: 25035496
2. H. Clevers, Modeling development and disease with organoids. Cell 165, 1586-1597 (2016). doi: 10.1016/j.cell.2016.05.082; pmid: 27315476
3. A. Fatehullah, S. H. Tan, N. Barker, Organoids as an in vitro model of human development and disease. Nat. Cell Biol. 18, 246-254 (2016). doi: 10.1038/ncb3312; pmid: 26911908
4. J. T. Neal, C. J. Kuo, Organoids as models for neoplastic transformation. Annu. Rev. Pathol. 11, 199-220 (2016). doi: 10.1146/annurev-pathol-012615-044249; pmid: 26907527
5. P. H. Dedhia, N. Bertaux-Skeirik, Y. Zavros, J. R. Spence, Organoid models of human gastrointestinal development and disease. Gastroenterology 150, 1098-1112 (2016). doi: 10.1053/j.gastro.2015.12.042; pmid: 26774180
6. J. Z. Johnson, D. Hockemeyer, Human stem cell-based disease modeling: Prospects and challenges. Curr. Opin. Cell Biol. 37, 84-90 (2015). doi: 10.1016/j.ceb.2015.10.007; pmid: 26546888
7. A. S. Daar, H. L. Greenwood, A proposed definition of regenerative medicine. J. Tissue Eng. Regen. Med. 1, 179-184 (2007). doi: 10.1002/term.20; pmid: 18038409
8. N. H. Franco, Animal experiments in biomedical research: A historical perspective. Animals 3, 238-273 (2013). doi: 10.3390/ani3010238; pmid: 26487317
9. R. Franco, A. Cedazo-Minguez, Successful therapies for Alzheimer's disease: Why so many in animal models and none in humans? Front. Pharmacol. 5, 146 (2014). doi: 10.3389/fphar.2014.00146; pmid: 25009496
10. M. van de Wetering et al., Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161, 933-945 (2015). doi: 10.1016/j.cell.2015.03.053; pmid: 25957691
11. J. F. Dekkers et al., Characterizing responses to CFTRmodulating drugs using rectal organoids derived from subjects with cystic fibrosis. Sci. Transl. Med. 8, 344ra84 (2016). doi: 10.1126/scitranslmed.aad8278; pmid: 27334259
12. F. L. B. Meijboom, E. N. Stassen, The End of Animal Life: A Start for Ethical Debate (Wageningen Academic Publishers, 2016).
13. P. Sandoe, N. H. Franco, T. B. Lund, D. M. Weary, I. A. S. Olsson, Harms to animals - can we agree on how best to limit them? ALTEX 4, 28-32 (2015).
14. S. Festing, R. Wilkinson, The ethics of animal research. Talking Point on the use of animals in scientific research. EMBO Rep. 8, 526-530 (2007). doi: 10.1038/sj.embor.7400993; pmid: 17545991
15. N. Gjorevski, A. Ranga, M. P. Lutolf, Bioengineering approaches to guide stem cell-based organogenesis. Development 141, 1794-1804 (2014). doi: 10.1242/dev.101048; pmid: 24757002
16. M. A. Lancaster, N. S. Corsini, T. R. Burkard, J. A. Knoblich, http://biorxiv.org/content/early/2016/04/19/049346 (2016).
17. R. J. Perry et al., Acetate mediates a microbiome-brain-b-cell axis to promote metabolic syndrome. Nature 534, 213-217 (2016). doi: 10.1038/nature18309; pmid: 27279214
18. I. A. S. Olsson, A. K. Hansen, P. Sandøe, Ethics and refinement in animal research. Science 317, 1680 (2007). doi: 10.1126/science.317.5845.1680; pmid: 17885114
19. D. V. Hansen, J. H. Lui, P. R. Parker, A. R. Kriegstein, Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature 464, 554-561 (2010). doi: 10.1038/nature08845; pmid: 20154730
20. T. J. Nowakowski et al., Expression analysis highlights AXL as a candidate Zika virus entry receptor in neural stem cells. Cell Stem Cell 18, 591-596 (2016). doi: 10.1016/j.stem.2016.03.012; pmid: 27038591
21. H. Retallack et al., http://biorxiv.org/content/early/2016/06/15/058883 (2016).
22. A. L. Bredenoord, G. Pennings, H. J. Smeets, G. de Wert, Dealing with uncertainties: Ethics of prenatal diagnosis and preimplantation genetic diagnosis to prevent mitochondrial disorders. Hum. Reprod. Update 14, 83-94 (2008). doi: 10.1093/humupd/dmm037; pmid: 18056133
23. B. Steinbock, Life Before Birth: The Moral and Legal Status of Embryos and Fetuses (Oxford Univ. Press, ed. 2, 2011).
24. The Congregation for the Doctrine of the Faith, Donum Vitae. Instruction on Respect for Human Life in Its Origin and the Dignity of Procreation (1987); www.vatican.va/roman-curia/congregations/cfaith/documents/rc-con-cfaith- doc-19870222-respect-for-human-life-en.html.
25. A. L. Bredenoord, P. Braude, Ethics of mitochondrial gene replacement: From bench to bedside. BMJ 341, c6021 (2010). doi: 10.1136/bmj.c6021; pmid: 21059727
26. I. Hyun, A. Wilkerson, J. Johnston, Embryology policy: Revisit the 14-day rule. Nature 533, 169-171 (2016). doi: 10.1038/533169a; pmid: 27172031
27. International Society for Stem Cell Research, Guidelines for Stem Cell Research and Clinical Translation (2016); www.isscr.org/docs/default-source/guidelines/isscr-guidelines-for-stemcell- research-and-clinical-translation.pdf?sfvrsn=2.
28. H. Tang et al., Zika virus infects human cortical neural progenitors and attenuates their growth. Cell Stem Cell 18, 587-590 (2016). doi: 10.1016/j.stem.2016.02.016; pmid: 26952870
29. X. Qian et al., Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165, 1238-1254 (2016). doi: 10.1016/j.cell.2016.04.032; pmid: 27118425
30. J. Dang et al., Zika virus depletes neural progenitors in human cerebral organoids through activation of the innate immune receptor TLR3. Cell Stem Cell 19, 258-265 (2016). doi: 10.1016/j.stem.2016.04.014; pmid: 27162029
31. F. R. Cugola et al., The Brazilian Zika virus strain causes birth defects in experimental models. Nature 534, 267-271 (2016). pmid: 27279226
32. S. N. Boers, J. J. M. van Delden, H. Clevers, A. L. Bredenoord, Organoid biobanking: Identifying the ethics: Organoids revive old and raise new ethical challenges for basic research and therapeutic use. EMBO Rep. 17, 938-941 (2016). pmid: 27296278
33. A. Deglincerti et al., Self-organization of the in vitro attached human embryo. Nature 533, 251-254 (2016). doi: 10.1038/nature17948; pmid: 27144363
34. M. N. Shahbazi et al., Self-organization of the human embryo in the absence of maternal tissues. Nat. Cell Biol. 18, 700-708 (2016). doi: 10.1038/ncb3347; pmid: 27144686
35. M. Mostert, A. L. Bredenoord, M. C. Biesaart, J. J. M. van Delden, Big Data in medical research and EU data protection law: Challenges to the consent or anonymise approach. Eur. J. Hum. Genet. 24, 1096 (2016). doi: 10.1038/ejhg.2016.71; pmid: 27307115
36. J. F. Dekkers et al., A functional CFTR assay using primary cystic fibrosis intestinal organoids. Nat. Med. 19, 939-945 (2013). doi: 10.1038/nm.3201; pmid: 23727931
37. N. A. A. Giesbertz, A. L. Bredenoord, J. J. M. van Delden, Inclusion of residual tissue in biobanks: Opt-in or opt-out? PLOS Biol. 10, e1001373 (2012). doi: 10.1371/journal. pbio.1001373; pmid: 22899893
38. S. N. Boers, J. J. M. van Delden, A. L. Bredenoord, Broad consent is consent for governance. Am. J. Bioeth. 15, 53-55 (2015). doi: 10.1080/15265161.2015.1062165; pmid: 26305756
39. K. C. O'Doherty et al., From consent to institutions: Designing adaptive governance for genomic biobanks. Soc. Sci. Med. 73, 367-374 (2011). doi: 10.1016/j.socscimed.2011.05.046; pmid: 21726926
40. E. Bender, "Science pic: Reprogramming a retina" (Novartis, 16 July 2015); www.nibr.com/stories/nerd-blog/science-picreprogramming- retina.
41. T. Ulrich, "Building brain organoids to shed light on disease" (Novartis, 20 May 2016); www.nibr.com/stories/nerd-blog/building-brain-organoids-shed-light-disease.
42. A. Ranga, N. Gjorevski, M. P. Lutolf, Drug discovery through stem cell-based organoid models. Adv. Drug Deliv. Rev. 69-70, 19-28 (2014). doi: 10.1016/j.addr.2014.02.006; pmid: 24582599
43. V. Marx, Tissue engineering: Organs from the lab. Nature 522, 373-377 (2015). doi: 10.1038/522373a; pmid: 26085275
44. M. Hild, A. B. Jaffe, Production of 3-D airway organoids from primary human airway basal cells and their use in highthroughput screening. Curr. Protoc. Stem Cell Biol. 37, IE.9.1-IE.9.15 (2016). pmid: 27171795
45. + stem cell. Nat. Med. 18, 618-623 (2012). doi: 10.1038/nm.2695; pmid: 22406745
46. M. Huch et al., Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160, 299-312 (2015). doi: 10.1016/j.cell.2014.11.050; pmid: 25533785
47. E. W. Kuijk et al., Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure. Sci. Rep. 6, 22154 (2016). doi: 10.1038/srep22154; pmid: 26915950
48. S. F. Boj et al., Organoid models of human and mouse ductal pancreatic cancer. Cell 160, 324-338 (2015). doi: 10.1016/j.cell.2014.12.021; pmid: 25557080
49. M. G. J. L. Habets, J. J. M. van Delden, S. L. Niemansburg, H. L. Atkins, A. L. Bredenoord, One size fits all? Ethical considerations for examining efficacy in first-in-human pluripotent stem cell studies. Mol. Ther. 24, 2039-2042 (2016). pmid: 27966562
50. FDA should stand firm on stem-cell treatments (Editorial). Nature 535, 7-8 (2016). doi: 10.1038/535007b
51. S. H. Woolf, The meaning of translational research and why it matters. JAMA 299, 211-213 (2008). doi: 10.1001/jama.2007.26; pmid: 18182604
52. S. L. Niemansburg, T. H. Tempels, W. J. Dhert, J. J. M. van Delden, A. L. Bredenoord, Societal impacts of regenerative medicine: Reflections on the views of orthopedic professionals. Regen. Med. 10, 17-24 (2015). doi: 10.2217/rme.14.69; pmid: 25562349
53. S. van der Burg, Taking the "soft impacts" of technology into account: Broadening the discourse in research practice. Soc. Epistemol. 23, 301-316 (2009). doi: 10.1080/02691720903364191
54. S. L. Niemansburg et al., Stem cell trials for cardiovascular medicine: Ethical rationale. Tissue Eng. A 20, 2567-2574 (2014). doi: 10.1089/ten.tea.2013.0332; pmid: 24164351
55. J. Kimmelman, Ethics, ambiguity aversion, and the review of complex translational clinical trials. Bioethics 26, 242-250 (2012). doi: 10.1111/j.1467-8519.2010.01856.x; pmid: 21241343
56. G. Schwank et al., Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell 13, 653-658 (2013). doi: 10.1016/j.stem.2013.11.002; pmid: 24315439
57. H. H. Bauer, Scientific Literacy and the Myth of the Scientific Method (Univ. of Illinois Press, 1992).
58. T. Kuhn, The Structure of Scientific Revolutions (Univ. of Chicago Press, 1962).
59. T. Swierstra, A. Rip, Nano-ethics as NEST-ethics: Patterns of moral argumentation about new and emerging science and technology. NanoEthics 1, 3-20 (2007). doi: 10.1007/s11569- 007-0005-8
60. T. Caulfield, D. Sipp, C. E. Murry, G. Q. Daley, J. Kimmelman, Confronting stem cell hype. Science 352, 776-777 (2016). doi: 10.1126/science.aaf4620; pmid: 27174977
61. E. Caldwell, "Scientist: Most complete human brain model to date is a 'brain changer'" (The Ohio State University, 18 August 2015); https://news.osu.edu/news/2015/08/18/human-brain-model/.
62. D. B. Resnik, A. E. Shamoo, The Singapore statement on research integrity. Account. Res. 18, 71-75 (2011). doi: 10.1080/08989621.2011.557296; pmid: 21390871
63. S. Chakradhar, New company aims to broaden researchers' access to organoids. Nat. Med. 22, 338 (2016). doi: 10.1038/nm0416-338; pmid: 27050584
64. A. Astashkina, D. W. Grainger, Critical analysis of 3-D organoid in vitro cell culture models for high-throughput drug candidate toxicity assessments. Adv. Drug Deliv. Rev. 69-70, 1-18 (2014). doi: 10.1016/j.addr.2014.02.008; pmid: 24613390