Ethical Issues in Tissue Engineering: A Systematic Review
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Abstract
This study examines, classifies and discusses the ethical issues of tissue engineering published in selected online databases from the year 2015 to 2020. In overview, the published literature could be classified according to the type of ethical issues discussed, the phase in development in which the ethical issues are prominently existing and into the type of journal they are published. It proceeds with in-depth discussions on selected relevant issues that deemed to be needing further attention and clarification. It will give the readers a broad mapping of ethical issues currently existing and discussed in the context of tissue engineering and highlights the conventional responses on the issues.
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Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: Explanation and elaboration. BMJ. 2009;339:b2700.
Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic Reviews. 2015;4(1):1–9.
Matthews KRW, Iltis AS. Unproven stem cell–based interventions and achieving a compromise policy among the multiple stakeholders. BMC Med Ethics. 2015;16(1):75.
Turner LG. US clinics marketing unproven and unlicensed adipose-derived autologous stem cell interventions. Regen Med. 2015;10(4):397–402.
Waldby C, Hendl T, Kerridge I, Lipworth W, Lysaght T, Munsie M, et al. The direct-to-consumer market for stem cell-based interventions in Australia: Exploring the experiences of patients. Regen Med. 2020;15(1):1238–1249.
Turner L, Knoepfler P. Selling Stem Cells in the USA: Assessing the Direct-to-Consumer Industry. Cell Stem Cell. 2016;19(2):154–157.
Datta S. An endogenous explanation of growth: Direct-to-consumer stem cell therapies in PR China, India and the USA. Regen Med. 2018;13(5):559–579.
Horner C, Tenenbaum E, Sipp D, Master Z. Can civil lawsuits stem the tide of direct-to-consumer marketing of unproven stem cell interventions. Npj Regenerative Medicine. 2018;3(1):5.
Knoepfler PS, Turner LG. The FDA and the US direct-to-consumer marketplace for stem cell interventions: A temporal analysis. Regen Med. 2018;13(1):19–27.
Turner L. Direct-to-consumer marketing of stem cell interventions by Canadian businesses. Regen Med. 2018;13(6):643–658.
Pean CA, Kingery MT, Strauss E, Bosco JA, Halbrecht J. Direct-to-Consumer Advertising of Stem Cell Clinics: Ethical Considerations and Recommendations for the Health-Care Community. J Bone Joint Surg Am. 2019;101(19):e103.
Jokura Y, Yano K, Yamato M. Comparison of the new Japanese legislation for expedited approval of regenerative medicine products with the existing systems in the USA and European Union. J Tissue Eng Regen Med. 2018;12(2):e1056–e1062.
Sawa Y. The ideal way to design clinical trials and establishment of evidence for human cellular and tissue-based products in Japan. J Tissue Eng Regen Med. 2019;13(6):905–907.
Ghinea N, Munsie M, Rudge C, Stewart C. Australian regulation of autologous human cell and tissue products: Implications for commercial stem cell clinics. Regen Med. 2020;15(2):1361–1369.
Daley GQ, Hyun I, Apperley JF, Barker RA, Benvenisty N, Bredenoord AL, et al. Setting Global Standards for Stem Cell Research and Clinical Translation: The 2016 ISSCR Guidelines. Stem Cell Reports. 2016;6(6):787–797.
Sipp D, Caulfield T, Kaye J, Barfoot J, Blackburn C, Chan S, et al. Marketing of unproven stem cell–based interventions: A call to action. Sci Transl Med. 2017;9(397):eaag0426.
Zarzeczny A, Atkins H, Illes J, Kimmelman J, Master Z, Robillard JM, et al. The stem cell market and policy options: A call for clarity. J Law Biosci. 2018;5(3):743–758.
Bauer G, Elsallab M, Abou-El-Enein M. Concise Review: A Comprehensive Analysis of Reported Adverse Events in Patients Receiving Unproven Stem Cell-Based Interventions: The Use of Unproven Stem Cell Interventions. Stem Cells Transl Med. 2018;7(9):676–685.
Kashihara H, Nakayama T, Hatta T, Takahashi N, Fujita M. Evaluating the Quality of Website Information of Private-Practice Clinics Offering Cell Therapies in Japan. Interact J Med Res. 2016;5(2):e15.
Munsie M, Lysaght T, Hendl T, Tan HYL, Kerridge I, Stewart C. Open for business: A comparative study of websites selling autologous stem cells in Australia and Japan. Regen Med. 2017;12(7):777–790.
Hawke B, Przybylo AR, Paciulli D, Caulfield T, Zarzeczny A, Master Z. How to Peddle Hope: An Analysis of YouTube Patient Testimonials of Unproven Stem Cell Treatments. Stem Cell Reports. 2019;12(6):1186–1189.
Rahman RA, Radzi MAA, Sukri NM, Nazir NM, Sha’ban M. Tissue engineering of articular cartilage: From bench to bed-side. Tissue Eng Regen Med. 2015;12(1):1–11.
Anton R. On recent advances in human engineering: Provocative trends in embryology, genetics, and regenerative medicine. Politics Life Sci. 2016;35(2):54–68.
Aznar J, Tudela J. Use of Embryonic Stem Cells to Treat Severe Eye Diseases. Cuad Bioet. 2016;27(90):241–247.
Faltus T, Storz U. Response to: Dittrich et al.: Non-Embryo-Destructive Extraction of Pluripotent Embryonic Stem Cells – Overlooked Legal Prohibitions, Professional Legal Consequences and Inconsistencies in Patent Law. Geburtshilfe Frauenheilkunde. 2016;76(12):1302–1307.
Sengupta P, Bhattacharya N, Bhattacharya S, Stubblefield PG. Ethics Pertaining to the Use of Aborted Human Tissues for Research and Therapeutic Purposes. In: Bhattacharya N, Stubblefield PG, editors. Springer International Publishing; 2016.
Sipp D, Pei D. No wild east. Nature. 2016;534:465–467.
Aach J, Lunshof J, Iyer E, Church GM. Addressing the ethical issues raised by synthetic human entities with embryo-like features. ELife. 2017;6:e20674.
Cyranoski D. Trials of embryonic stem cells to launch in China. Nature. 2017;546(7656):15–16.
Farajkhoda T. An overview on ethical considerations in stem cell research in Iran and recommendations: A review. Int J Reprod Biomed. 2017;15(2):67–74.
Hurlbut JB, Hyun I, Levine AD, Lovell-Badge R, Lunshof JE, Matthews KRW, et al. Revisiting the Warnock rule. Nature Biotechnology. 2017;35(11):1029–1042.
Storz U, Faltus T. Patent eligibility of stem cells in Europe: Where do we stand after 8 years of case law?. Regen Med. 2017;12(1):37–51.
Ogbogu U, Zarzeczny A, Balt J, Bedford P, Du J, Hyun I, et al. Research on Human Embryos and Reproductive Materials: Revisiting Canadian Law and Policy. Healthc Policy. 2018;13(3):10–19.
Shen H. Researchers are starting to demystify the earliest stages of human development—Edging right up to an ethical red line. Nature. 2018;559:19–22.
Volarevic V, Markovic BS, Gazdic M, Volarevic A, Jovicic N, Arsenijevic N, et al. Ethical and Safety Issues of Stem Cell-Based Therapy. Int J Med Sci. 2018;15(1):36–45.
Zamborsky R, Kilian M, Csobonyeiova M, Danisovic L. Regenerative Medicine in Orthopaedics and Trauma: Challenges, Regulation and Ethical Issues. Ortop Traumatol Rehabil. 2018;20(3):173–180.
Nawab K, Bhere D, Bommarito A, Mufti M, Naeem A. Stem Cell Therapies: A Way to Promising Cures. Cureus. 2019;11(9):e5712.
Jonlin EC. Informed Consent for Human Embryo Genome Editing. Stem Cell Reports. 2020;14(4):530–537.
Moy A. Creating Catholic Regenerative Medicine Organizations in a Secular Biotechnology Field: A Physician-Scientist Experience. Linacre Q. 2020;87(2):218–222.
Veiga A, Aran B, Raya A, Messinis I, Mahmood T. EBCOG position statement: Ethics of stem cell research. Eur J Obstet Gynecol Reprod Biol. 2020;247:244–245.
Kashi A, Saha S. Ethical/Legal Aspects of Tissue Engineered Products. In: Vishwakarma A, Sharpe P, Shi S, Ramalingam M. Academic Press; 2015.
Porteus M. Genome Editing: A New Approach to Human Therapeutics. Annu Rev Pharmacol Toxicol. 2016;56(1):163–190.
Chan S. Current and emerging global themes in the bioethics of regenerative medicine: The tangled web of stem cell translation. Regen Med. 2017;12(7):839–851.
Ilic D, Ogilvie C, Noli L, Kolundzic N, Khalaf Y. Human embryos from induced pluripotent stem cell-derived gametes: Ethical and quality considerations. Regen Med. 2017;12(6):681–691.
Master Z, Bedford P. CRISPR Gene Editing Should Be Allowed in Canada, But Under What Circumstances?. J Obstet Gynaecol Can. 2018;40(2):224–226.
Dzilic E, Lahm H, Dreßen M, Deutsch M-A, Lange R, Wu SM, et al. Genome Editing Redefines Precision Medicine in the Cardiovascular Field. Stem Cells International. 2018;2018:1–11.
Roh DS, Li EB-H, Liao EC. CRISPR Craft: DNA Editing the Reconstructive Ladder. Plast Reconstr Surg. 2018;142(5):1355–1364.
Chapman AR. What can we learn from California Institute for Regenerative Medicine’s first 50 clinical trials?. Regen Med. 2019;14(10):899–903.
Goodarzi P, Falahzadeh K, Aghayan H, Payab M, Larijani B, Alavi-Moghadam S, et al. Therapeutic abortion and ectopic pregnancy: Alternative sources for fetal stem cell research and therapy in Iran as an Islamic country. Cell Tissue Bank. 2019;20(1):11–24.
McCune JM, Weissman IL. The Ban on US Government Funding Research Using Human Fetal Tissues: How Does This Fit with the NIH Mission to Advance Medical Science for the Benefit of the Citizenry?. Stem Cell Reports. 2019;13(5):777–786.
Meagher KM, Master Z. Fostering a prevention mindset for responsible gene editing. Accountability Res. 2019;26(4):251–256.
Mikkelsen RB, Frederiksen HRS, Gjerris M, Holst B, Hyttel P, Luo Y, et al. Genetic Protection Modifications: Moving Beyond the Binary Distinction Between Therapy and Enhancement for Human Genome Editing. The CRISPR Journal. 2019;2(6):362–369.
Sharma A, Scott CT. The ethics of publishing human germline research. Nature Biotechnology. 2015;33(6):590–593.
Vassena R, Heindryckx B, Peco R, Pennings G, Raya A, Sermon K, et al. Genome engineering through CRISPR/Cas9 technology in the human germline and pluripotent stem cells. Hum Reprod Update. 2016;22(4):411–419.
Waddington SN, Privolizzi R, Karda R, O’Neill HC. A Broad Overview and Review of CRISPR-Cas Technology and Stem Cells. Current Stem Cell Reports. 2016;2(1):9–20.
Harper JC, Aittomäki K, Borry P, Cornel MC, de Wert G, Dondorp W, et al. Recent developments in genetics and medically assisted reproduction: From research to clinical applications. Eur J Hum Genet. 2018;26(1):12–33.
Meagher KM, Allyse MA, Master Z, Sharp RR. Reexamining the Ethics of Human Germline Editing in the Wake of Scandal. Mayo Clinic Proceedings. 2020;95(2):330–338.
Mansnérus JA. Bioethical and legal perspectives on cell reprogramming technologies. Medical Law International. 2016;16(3–4):206–228.
Temple S, Goldstein LSB. Why we need fetal tissue research. Science. 2019;363(6424):207–207.
Segers S, Mertes H, de Wert G, Dondorp W, Pennings G. Balancing Ethical Pros and Cons of Stem Cell Derived Gametes. Ann Biomed Eng. 2017;45(7):1620–1632.
Advena-Regnery B, Dederer H-G, Enghofer F, Cantz T, Heinemann T. Framing the ethical and legal issues of human artificial gametes in research, therapy, and assisted reproduction: A German perspective. Bioethics. 2018;32(5):314–326.
Fung RKF, Kerridge IH. Gene editing advance re-ignites debate on the merits and risks of animal to human transplantation: Gene editing and xenotransplantation. Intern Med J. 2016;46(9):1017–1022.
Wu J, Greely HT, Jaenisch R, Nakauchi H, Rossant J, Belmonte JCI. Stem cells and interspecies chimaeras. Nature. 2016;540(7631):51–59.
Masaki H, Nakauchi H. Interspecies chimeras for human stem cell research. Development. 2017;144(14):2544–2547.
Garry MG, Garry DJ. Humanized organs in gene-edited animals. Regen Med. 2016;11(7):617–619.
Mascetti VL, Pedersen RA. Contributions of Mammalian Chimeras to Pluripotent Stem Cell Research. Cell Stem Cell. 2016;19(2):163–175.
Sharma A, Sebastiano V, Scott CT, Magnus D, Koyano-Nakagawa N, Garry DJ, et al. Lift NIH restrictions on chimera research. Science. 2015;350(6261):640.
Inoue Y, Shineha R, Yashiro Y. Current Public Support for Human-Animal Chimera Research in Japan Is Limited, Despite High Levels of Scientific Approval. Cell Stem Cell. 2016;19(2):152–153.
Raman R, Bashir R. Biomimicry, Biofabrication, and Biohybrid Systems: The Emergence and Evolution of Biological Design. Adv Healthc Mater. 2017;6(20):1700496.
Nishiwaki S. Rules of providing cord blood for induced pluripotent stem cells for research. Cytotherapy. 2015;17(7):1008.
Reilly J, Gallagher L, Chen JL, Leader G, Shen S. Bio-collections in autism research. Molecular Autism. 2017;8(1):34.
Ooi L, Dottori M, Cook AL, Engel M, Gautam V, Grubman A, et al. If Human Brain Organoids Are the Answer to Understanding Dementia, What Are the Questions?. Neuroscientist. 2020;26(5–6):438–454.
King NMP. Key Information in the New Common Rule: Can It Save Research Consent?. The Journal of Law, Medicine & Ethics. 2019;47(2):203–212.
Hug K, Johansson M. The ethics of withdrawal: The case of follow-up from first-in-human clinical trials. Regen Med. 2017;12(1):25–36.
Bredenoord AL, Mostert M, Isasi R, Knoppers BM. Data sharing in stem cell translational science: Policy statement by the International Stem Cell Forum Ethics Working Party. Regen Med. 2015;10(7):857–861.
Morrison M, Moraia LB, Steele JC. Traceability in stem cell research: From participant sample to induced pluripotent stem cell and back. Regen Med. 2016;11(1):73–79.
Moradi S, Mahdizadeh H, Šarić T, Kim J, Harati J, Shahsavarani H, et al. Research and therapy with induced pluripotent stem cells (iPSCs): Social, legal, and ethical considerations. Stem Cell Res Ther. 2019;10(1):341.
Sipp D. Identity and ownership issues in the regulation of autologous cells. Regen Med. 2017;12(7):827–838.
Ballen KK, Verter F, Kurtzberg J. Umbilical cord blood donation: Public or private?. Bone Marrow Transplant. 2015;50(10):1271–1278.
de Vries RBM, Leenaars M, Tra J, Huijbregtse R, Bongers E, Jansen JA, et al. The potential of tissue engineering for developing alternatives to animal experiments: A systematic review: Tissue-engineered alternatives. J Tissue Eng Regen Med. 2015;9(7):771–778.
Moran CJ, Ramesh A, Brama PAJ, O’Byrne JM, O’Brien FJ, & Levingstone TJ. The benefits and limitations of animal models for translational research in cartilage repair. J Exp Orthop. 2016;3(1):1–12.
Cheluvappa R, Scowen P, Eri R. Ethics of animal research in human disease remediation, its institutional teaching; and alternatives to animal experimentation. Pharmacol Res Perspect. 2017;5(4):e00332.
Liguori GR, Jeronimus BF, de Aquinas Liguori TT, Moreira LFP, Harmsen MC. Ethical Issues in the Use of Animal Models for Tissue Engineering: Reflections on Legal Aspects, Moral Theory, Three Rs Strategies, and Harm–Benefit Analysis. Tissue Eng Part C Methods. 2017;23(12):850–862.
Bonniaud P, Fabre A, Frossard N, Guignabert C, Inman M, Kuebler WM, et al. Optimising experimental research in respiratory diseases: An ERS statement. Eur Respir J. 2018;51(5):1702133.
Coy RH, Evans OR, Phillips JB, Shipley RJ. An integrated theoretical-experimental approach to accelerate translational tissue engineering. J Tissue Eng Regen Med. 2018;12(1):e53–e59.
Lucas-Samuel S, Ferry N, Trouvin J-H. Overview of the Regulatory Oversight Implemented by the French Regulatory Authorities for the Clinical Investigation of Gene Therapy and Cell Therapy Products. In: Galli MC, Serabian M, editors. Springer International Publishing; 2015.
Niemansburg SL, Habets MGJL, Dhert WJA, van Delden JJM, Bredenoord AL. Participant selection for preventive Regenerative Medicine trials: Ethical challenges of selecting individuals at risk. J Med Ethics. 2015;41(11):914–916.
Mwaka E. Ethical Issues in Translational Research: From the Bench to Theatre. Annals of African Surgery. 2016;13(2):42–44.
Rosemann A, Sleeboom-Faulkner M. New regulation for clinical stem cell research in China: Expected impact and challenges for implementation. Regen Med. 2016;11(1):5–9.
Takashima K, Inoue Y, Tashiro S, Muto K. Lessons for reviewing clinical trials using induced pluripotent stem cells: Examining the case of a first-in-human trial for age-related macular degeneration. Regen Med. 2018;13(2):123–128.
King NMP, Bishop CE. How Should Physicians Help Patients Understand Unknowns of Nanoparticle-Based Medicines?. AMA Journal of Ethics. 2019;21(4):E324–331.
Hayakawa T, Aoi T, Umezawa A, Ozawa K, Sato Y, Sawa Y, et al. A study on ensuring the quality and safety of pharmaceuticals and medical devices derived from processing of allogeneic human induced pluripotent stem(-Like) cells. Regen Ther. 2015;2:95–108.
Barker RA, Carpenter MK, Forbes S, Goldman SA, Jamieson C, Murry CE, et al. The Challenges of First-in-Human Stem Cell Clinical Trials: What Does This Mean for Ethics and Institutional Review Boards?. Stem Cell Reports. 2018;10(5):1429–1431.
Kleiderman E, Boily A, Hasilo C, Knoppers BM. Overcoming barriers to facilitate the regulation of multi-centre regenerative medicine clinical trials. Stem Cell Res Ther. 2018;9(307):1–9.
Warren M. U.K. trials of airway transplants are in limbo. Science. 2018;359(6383):1448–1450.
Fung M, Yuan Y, Atkins H, Shi Q, Bubela T. Responsible Translation of Stem Cell Research: An Assessment of Clinical Trial Registration and Publications. Stem Cell Reports. 2017;8(5):1190–1201.
Niemansburg SL, van Delden JJM, Dhert WJA, Bredenoord AL. Reconsidering the ethics of sham interventions in an era of emerging technologies. Surgery. 2015;157(4):801–810.
de Windt TS, Niemansburg SL, Vonk LA, van Delden JM, Roes KCB, Dhert WJA, et al. Ethics in musculoskeletal regenerative medicine; guidance in choosing the appropriate comparator in clinical trials. Osteoarthritis and Cartilage. 2019;27(1):34–40.
Zvonareva O, Pimenov I, Kutishenko N, Mareev I, Martsevich S, Kulikov E. Informal professionalization of healthy participants in phase I clinical trials in Russia. Clinical Trials. 2019;16(6):563–570.
Turner L. ClinicalTrials.gov, stem cells and ‘pay-to-participate’ clinical studies. Regen Med. 2017;12(6):705–719.
Wagner DE, Turner L, Panoskaltsis-Mortari A, Weiss DJ, Ikonomou, L. Co-opting of ClinicalTrials.gov by patient-funded studies. Lancet Respir Med. 2018;6(8):579–581.
Rose JB, May M, Williams DJ. Determinants of clinician adoption of regenerative therapies in the UK and Canada: An ophthalmology perspective. Regen Med. 2015;10(4):481–493.
De Salvatore S, Segreto A, Chiusaroli A, Congiu S, Bizzarri F. The Role of Xenotransplantation in Cardiac Transplantation: Xenotransplantation in Cardiac Surgery. J Card Surg. 2015;30(1):111–116.
Rao M, Mason C, Solomon S. Cell therapy worldwide: An incipient revolution. Regen Med. 2015;10(2):181–191.
Zettler PJ. Compassionate use of experimental therapies: Who should decide?. EMBO Mol Med. 2015;7(10):1248–1250.
Cossu G, Buccione R, De Luca M. A discussion on cell therapy in Manchester. Stem Cell Research. 2016;16(3):614–616.
Fujita M, Hatta T, Ozeki R, Akabayashi A. The current status of clinics providing private practice cell therapy in Japan. Regen Med. 2016;11(1):23–32.
Nakazawa E, Takimoto Y, Akabayashi A. The Social Framework Surrounding the Development of Regenerative Medicine in Japan. Camb Q Healthc Ethics. 2016;25(3):466–471.
Brooks M. Stem cell research: Time for a dose of realism. BMJ. 2017;356:j443.
Sipp D. Cell Churches and Stem Cell Marketing in South Korea and the United States. Developing World Bioethics. 2017;17(3):167–172.
von Tigerstrom B. Regulating the advertising and promotion of stem cell therapies. Regen Med. 2017;12(7):815–826.
Julian K, Yuhasz N, Hollingsworth E, Imitola J. The “Growing” Reality of the Neurological Complications of Global “Stem Cell Tourism.” Seminars in Neurology. 2018;38(02):176–181.
Knoepfler PS. Mapping and driving the stem cell ecosystem. Regen Med. 2018;13(7):845–858.
Sugarman J, Barker RA, Kerridge I, Lysaght T, Pellegrini G, Sipp D, et al. Tackling Ethical Challenges of Premature Delivery of Stem Cell-Based Therapies: ISSCR 2018 Annual Meeting Focus Session Report. Stem Cell Reports. 2018;11(5):1021–1025.
Loring JF. Wind-down of stem-cell institute leaves a void. Nature. 2019;572(7768):155–155.
Zocchi ML, Vindigni V, Pagani A, Pirro O, Conti G, Sbarbati A, et al. Regulatory, ethical, and technical considerations on regenerative technologies and adipose-derived mesenchymal stem cells. Eur J Plast Surg. 2019;42(6):531–548.
Ikka T, Fujita M, Yashiro Y, Ikegaya H. Recent Court Ruling in Japan Exemplifies Another Layer of Regulation for Regenerative Therapy. Cell Stem Cell. 2015;17(5):507–508.
Snyder J, Turner L. Selling stem cell ‘treatments’ as research: Prospective customer perspectives from crowdfunding campaigns. Regen Med. 2018;13(4):375–384.
Prasad A. Resituating overseas stem cell therapy. Regen Med. 2017;12(7):743–748.
Knoepfler PS. From bench to FDA to bedside: US regulatory trends for new stem cell therapies. Adv Drug Deliv Rev. 2015;82–83:192–196.
Pinheiro LL, de Lima AR, Branco É. Is Stem Cell Commerce in Small Animal Therapies Scientifically and Morally Justified?. Stem Cell Rev Rep. 2019;15(4):506–518.
The Lancet. Paolo Macchiarini is not guilty of scientific misconduct. The Lancet. 2015;386(9997):932.
Vogel G. Report finds misconduct by surgeon. Science. 2015;348(6238):954–955.
Vogel G. Trachea surgeon cleared of misconduct. Science. 2015;349(6252):1035–1035.
Hawkes N. Nobel official resigns in wake of storm over Italian surgeon. BMJ. 2016;352:i837.
Hörnlund A. Clarification regarding ethical review of Paolo Macchiarini’s research. The Lancet. 2016;387(10030):1816.
Vogel G. Former star surgeon’s disgrace rocks Swedish science. Science. 2016;353(6305):1193–1194.
Astakhova A. Paolo Macchiarini’s academic afterlife in Russia ends. Science. 2017;356(6339):672–673.
Gilbert F, Viaña JNM, O’Connell CD, Dodds S. Enthusiastic portrayal of 3D bioprinting in the media: Ethical side effects. Bioethics. 2018;32(2):94–102.
Zarzeczny A, Tanner C, Barfoot J, Blackburn C, Couturier A, Munsie M. Contact us for more information: An analysis of public enquiries about stem cells. Regen Med. 2019;14(12):1137–1150.
Tanner C, Petersen A, Munsie M. ‘No one here’s helping me, what do you do?’: Addressing patient need for support and advice about stem cell treatments. Regen Med. 2017;12(7):791–801.
Harris DT. Banking of Adipose- and Cord Tissue-Derived Stem Cells: Technical and Regulatory Issues. In: Karimi-Busheri F, Weinfeld M, editors. Springer International Publishing; 2016.
Chang H-C. The role of policies and networks in development of cord blood usage in China. Regen Med. 2017;12(6):637–645.
Morrison M, Bell J, George C, Harmon S, Munsie M, Kaye J. The European General Data Protection Regulation: Challenges and considerations for iPSC researchers and biobanks. Regen Med. 2017;12(6):693–703.
Lensink MA, Jongsma KR, Boers SN, Noordhoek JJ, Beekman JM, Bredenoord AL. Responsible use of organoids in precision medicine: The need for active participant involvement. Development. 2020;147(7):dev177972.
Carr DR, Bradshaw SE. Gene therapies: The challenge of super-high-cost treatments and how to pay for them. Regen Med. 2016;11(4):381–393.
Bubela T, McCabe C, Archibald P, Atkins H, Bradshaw SE, Kefalas P, et al. Bringing regenerative medicines to the clinic: The future for regulation and reimbursement. Regen Med. 2015;10(7):897–911.
Arjmand B, Larijani B, Sheikh Hosseini M, Payab M, Gilany K, Goodarzi P, et al. The Horizon of Gene Therapy in Modern Medicine: Advances and Challenges. In: Turksen K, editor. Springer, Cham; 2019.
Spinner DS, Faulkner EC, Carroll MC, Ringo MC, Joines JW. Regenerative Medicine and Cell Therapy in Orthopedics—Health Policy, Regulatory and Clinical Development, and Market Access. Techniques in Orthopaedics. 2019;34(4):224–243.
Salmikangas P, Schuessler-Lenz M, Ruiz S, Celis P, Reischl I, Menezes-Ferreira M, et al. Marketing Regulatory Oversight of Advanced Therapy Medicinal Products (ATMPs) in Europe: The EMA/CAT Perspective. In: Galli MC, Serabian M, editors. Springer International Publishing; 2015.
Roura S, Gálvez-Montón C, Mirabel C, Vives J, Bayes-Genis A. Mesenchymal stem cells for cardiac repair: Are the actors ready for the clinical scenario?. Stem Cell Res Ther. 2017;8(238):1–11.
Ravnic DJ, Leberfinger AN, Koduru SV, Hospodiuk M, Moncal KK, Datta P, et al. Transplantation of Bioprinted Tissues and Organs: Technical and Clinical Challenges and Future Perspectives. Annals of Surgery. 2017;266(1):48–58.
Radzi MAA, Hashi AA, Sha’ban M. An Overview of the Application of Maqasid Al-Shariah into Cartilage Tissue Engineering. IIUM Medical Journal Malaysia. 2018;17(1):151–156.
Kemaloglu C, Birtek F. A general evaluation of stem cell studies and human cloning from the ethical, faith, and legal perspective. Turk J Plast Surg. 2019;27(1):3–8.
Almarzouq F, Rennekampff H, Almarzouki M, Lambertz A, Acharya M, Klink C, et al. Porcine-Derived Biomaterials in Tissue Engineering and Reconstructive Surgery: Considerations and Alternatives in Muslim Patients. J Tissue Eng Regen Med. 2018;13(2):253–260.
Cooper DKC. The case for xenotransplantation. Clin Transplant. 2015;29(4):288–293.
Dolgin E. Core Concept: Chimeras keep courting controversy. Proceedings of the National Academy of Sciences. 2016;113(43):11984–11985.
Shaw D, Dondorp W, Geijsen N, de Wert G. Creating human organs in chimaera pigs: An ethical source of immunocompatible organs?. J Med Ethics. 2015;41(12):970–974.
Bourret R, Martinez E, Vialla F, Giquel C, Thonnat-Marin A, De Vos J. Human–animal chimeras: Ethical issues about farming chimeric animals bearing human organs. Stem Cell Res Ther. 2016;7(1):87.
Sawai T, Hatta T, Fujita M. Public attitudes in Japan towards human–animal chimeric embryo research using human induced pluripotent stem cells. Regen Med. 2017;12(3):233–248.
Chen HI, Wolf JA, Blue R, Song MM, Moreno JD, Ming G, et al. Transplantation of Human Brain Organoids: Revisiting the Science and Ethics of Brain Chimeras. Cell Stem Cell. 2019;25(4):462–472.
Crane AT, Voth JP, Shen FX, Low WC. Concise Review: Human-Animal Neurological Chimeras: Humanized Animals or Human Cells in an Animal?: Human-Animal Neurological Chimeras. Stem Cells. 2019;37(4):444–452.
Garry DJ, Caplan AL, Garry MG. Chimeric Humanized Vasculature and Blood: The Intersection of Science and Ethics. Stem Cell Reports. 2020;14(4):538–540.
Tarifa CM, Navas LL, Azkona G, Pernaute RS. Chimeras for the twenty-first century. Crit Rev Biotechnol. 2020;40(3):283–291.
Furr A, Hardy MA, Barret JP, Barker JH. Surgical, ethical, and psychosocial considerations in human head transplantation. Int J Surg. 2017;41:190–195.
Gardner J. Distributive justice and regenerative medicine. Regen Med. 2017;12(7):865–874.
Andrews P, Baker D, Benvinisty N, Miranda B, Bruce K, Brüstle O, et al. Points to consider in the development of seed stocks of pluripotent stem cells for clinical applications: International Stem Cell Banking Initiative (ISCBI). Regen Med. 2015;10(2s):1–44.
Bayon Y, Vertès AA, Ronfard V, Culme-Seymour E, Mason C, Stroemer P, et al. Turning Regenerative Medicine Breakthrough Ideas and Innovations into Commercial Products. Tissue Eng Part B Rev. 2015;21(6):560–571.
de Freitas DRC. The Regulatory Pathway for Advanced Cell Therapy and Gene Therapy Products in Brazil: A Road to Be Built. In: Galli MC, Serabian M, editors. Springer International Publishing; 2015.
Gardner J, Faulkner A, Mahalatchimy A, Webster A. Are there specific translational challenges in regenerative medicine? Lessons from other fields. Regen Med. 2015;10(7):885–895.
Griffin M, Salmasi S, Naderi N, Butler PE, Seifalian AM. Advancing Translational Nanotechnology to Clinical Application. In: Baharvand H, Aghdami N, editors. John Wiley & Sons, Inc; 2015.
Hasegawa K, Asada T, Sengoku S, Nakatsuji N. World Stem Cell Summit 2014. Regen Med. 2015;10(4):393–396.
Lowenthal J, Sugarman J. Ethics and Policy Issues for Stem Cell Research and Pulmonary Medicine. Chest. 2015;147(3):824–834.
Lu L, Arbit HM, Herrick JL, Segovis SG, Maran A, Yaszemski MJ. Tissue Engineered Constructs: Perspectives on Clinical Translation. Ann Biomed Eng. 2015;43(3):796–804.
Maeda D, Yamaguchi T, Ishizuka T, Hirata M, Takekita K, Sato D. Regulatory Frameworks for Gene and Cell Therapies in Japan. In: Galli MC, Serabian M, editors. Springer International Publishing; 2015.
Murphy SV, Atala A. New Government Accountability Office Report on Regenerative Medicine Provides an Excellent Assessment of the Field: Accountability Report on Regenerative Medicine. Stem Cells Transl Med. 2015;4(12):1371–1372.
Rafiq QA, Ortega I, Jenkins SI, Wilson SL, Patel AK, Barnes AL, et al. The early career researcher’s toolkit: Translating tissue engineering, regenerative medicine and cell therapy products. Regen Med. 2015;10(8):989–1003.
Senatore V, Scott CT, Sebastiano V. Patenting parthenotes in the US and Europe. Nat Biotechnol. 2015;33(12):1232–1234.
Sipp D. Conditional Approval: Japan Lowers the Bar for Regenerative Medicine Products. Cell Stem Cell. 2015;16(4):353–356.
Viswanathan S, Bubela T. Current practices and reform proposals for the regulation of advanced medicinal products in Canada. Regen Med. 2015;10(5):647–663.
Habets MG, van Delden JJ, Bredenoord AL. Studying the lay of the land: Views and experiences of professionals in the translational pluripotent stem cell field. Regen Med. 2016;11(1):63–71.
Kemp P. Regenerative medicine: Looking backward 10 years further on. Regen Med. 2016;11(8):787–800.
Lysaght T, Sugii S. Uncertain Oversight of Regenerative Medicines in Japan under the ASRM. Cell Stem Cell. 2016;18(4):438–439.
Morrison S. Advancing Stem Cell Science and Translation. Stem Cell Reports. 2016;6(6):785–786.
Rosemann A, Bortz G, Vasen F, Sleeboom-Faulkner M. Global regulatory developments for clinical stem cell research: Diversification and challenges to collaborations. Regen Med. 2016;11(7):647–657.
Aghayan HR, Arjmand B, Ahmadbeigi N, Gheisari Y, Vasei M. Draft of Iranian National Guideline for Cell Therapy Manufacturing. Arch Iran Med. 2017;20(8):547–550.
Bachtarzi H. Ex vivo and in vivo genome editing: A regulatory scientific framework from early development to clinical implementation. Regen Med. 2017;12(8):1015–1030.
Barfoot J, Rosemann A, Blackburn CC. Special focus issue on regenerative medicine in society: Interdisciplinary perspectives (part II) - Foreword. Regen Med. 2017;12(7):733–736.
Barfoot J, Doherty K, Blackburn CC. EuroStemCell: A European infrastructure for communication and engagement with stem cell research. Seminars in Cell & Developmental Biology. 2017;70:26–37.
Chen H. Reflection on the governance of clinical stem cell research and applications in China. Regen Med. 2017;12(6):593–597.
Hogle LF, Das A. The social production of evidence: Regenerative medicine and the 21st Century Cures Act. Regen Med. 2017;12(6):581–586.
Levin LA, Miller JW, Zack DJ, Friedlander M, Smith LEH. Special Commentary: Early Clinical Development of Cell Replacement Therapy: Considerations for the National Eye Institute Audacious Goals Initiative. Ophthalmology. 2017;124(7):926–934.
Mahalatchimy A, Faulkner A. The emerging landscape of reimbursement of regenerative medicine products in the UK: Publications, policies and politics. Regen Med. 2017;12(6):611–622.
Rosemann A, Barfoot J, Blackburn C. Special focus issue on regenerative medicine in society: Interdisciplinary perspectives (part I) – Foreword. Regen Med. 2017;12(6):577–580.
Tiwari SS, Raman S, Martin P. Regenerative medicine in India: Trends and challenges in innovation and regulation. Regen Med. 2017;12(7):875–885.
Webster A. Regenerative medicine and responsible research and innovation: Proposals for a responsible acceleration to the clinic. Regen Med. 2017;12(7):853–864.
Zarzeczny A, McNutt K. Wicked policy issues in regenerative medicine and the need to explore new avenues for public engagement. Regen Med. 2017;12(7):749–752.
Zhang JY. Lost in translation? Accountability and governance of clinical stem cell research in China. Regen Med. 2017;12(6):647–656.
Akabayashi A, Nakazawa E, Jecker NS. Endangerment of the iPSC stock project in Japan: On the ethics of public funding policies. Journal of Medical Ethics. 2018;44(10):700–702.
Beck S. Getting up close and personal with UK genomics and beyond. Genome Med. 2018;10(1):38.
Bin Abdul Aziz MF, Morrison M, Kaye J. Regulating human stem cell research and therapy in low- and middle-income countries: Malaysian perspectives. New Genetics and Society. 2018;37(1):2–20.
Chan S. Research Translation and Emerging Health Technologies: Synthetic Biology and Beyond. Health Care Anal. 2018;26(4):310–325.
Hauskeller C. Between the Local and the Global: Evaluating European regulation of stem cell regenerative medicine. Perspect Biol Med. 2018;61(1):42–58.
Jaenisch R, Dubois N, Rasko JEJ, Hongkui D, Alvarado AS, Fuchs E, et al. Challenging Stem Cells. Cell. 2018;173(5):1063–1065.
Keller GS. Biologic Treatments Are Our Future, but a More Regulated One. Facial Plast Surg Clin North Am. 2018;26(4):ix–xi.
Paradise J. 21st Century Citizen Pharma: The FDA & Patient-Focused Product Development. American Journal of Law & Medicine. 2018;44(2–3):309–327.
Sleeboom-Faulkner M, Chen H, Rosemann A. Regulatory capacity building and the governance of clinical stem cell research in China. Science and Public Policy. 2018;45(3):416–427.
Bubela T, Kleiderman E, Master Z, et al. Canada’s Assisted Human Reproduction Act: Pragmatic Reforms in Support of Research. Front Med (Lausanne). 2019;6:157.
Li Y, Verter F, Wang B, Gu N. Regulations on cell therapy products in China: A brief history and current status. Regen Med. 2019;14(8):791–803.
O’Donnell BT, Ives CJ, Mohiuddin OA, Bunnell BA. Beyond the Present Constraints That Prevent a Wide Spread of Tissue Engineering and Regenerative Medicine Approaches. Front Bioeng Biotechnol. 2019;7:95.
Shapiro SA, Smith CG, Arthurs JR, Master Z. Preparing regenerative therapies for clinical application: Proposals for responsible translation. Regen Med. 2019;14(2):77–84.
Sleeboom-Faulkner M. Regulatory brokerage: Competitive advantage and regulation in the field of regenerative medicine. Soc Stud Sci. 2019;49(3):355–380.
Choudhury D, Ashok A, Naing MW. Commercialization of Organoids. Trends in Molecular Medicine. 2020;26(3):245–249.
Oberweis CV, Marchal JA, López-Ruiz E, Gálvez-Martín P. A Worldwide Overview of Regulatory Frameworks for Tissue-Based Products. Tissue Eng Part B Rev. 2020;26(2):181–196.
Hostiuc S, Rusu MC, Negoi I, Perlea P, Dorobanţu B, Drima E. The moral status of cerebral organoids. Regenerative Therapy. 2019;10:118–122.
Alexiou A, Simou P, Alexiou F, Chatzichronis S, Ashraf GM. Social and Ethical Impact of Advanced Artificial and Biological Enhancements. The Open Public Health Journal. 2020;13(1):62–68.
Harbaugh JT. Do You Own Your 3D Bioprinted Body? Analyzing Property Issues at the Intersection of Digital Information and Biology. Am J Law Med. 2015;41(1):167–189.
Hornick JF, Rajan K. Intellectual property in 3D printing and nanotechnology. In: Zhang LG, Fisher JP, Leong KW. Academic Press; 2015.
Benatar D. Bioethics and health and human rights: A critical view. J Med Ethics. 2006;32(1):17–20.
Knoepffler N, Spranger TM, Münch N, O’Malley M. Ethics and Law in Regenerative Medicine. In: Steinhoff G, editor. Springer International Publishing; 2016.
Kohn DB, Porteus MH, Scharenberg AM. Ethical and regulatory aspects of genome editing. Blood. 2016;127(21):2553–2560.
Illes J, Sipp D, Kleiderman E, Benjaminy S, Isasi R, Lomax G, et al. A blueprint for the next generation of ELSI research, training, and outreach in regenerative medicine. Npj Regenerative Medicine. 2017;2(1):21.
Lysaght T. Accelerating regenerative medicine: The Japanese experiment in ethics and regulation. Regen Med. 2017;12(6):657–668.
Martinho AM, Turner L. Stem cells in court: Historical trends in US legal cases related to stem cells. Regen Med. 2017;12(4):419–430.
Smith CM. Origin and uses of primum non nocere--above all, do no harm!. J Clin Pharmacol. 2005;45(4):371–377.
Lysaght MJ. Product Development in Tissue Engineering. Tissue Engineering. 1995;1(2):221–228.
Lysaght MJ, Nguy NAP, Sullivan K. An Economic Survey of the Emerging Tissue Engineering Industry. Tissue Engineering. 1998;4(3):231–238.
Lysaght MJ, Reyes J. The Growth of Tissue Engineering. Tissue Engineering. 2001;7(5):485–493.
Lysaght MJ, Hazlehurst AL. Tissue Engineering: The End of the Beginning. Tissue Engineering. 2004;10(1–2):309–320.
Lysaght MJ, Jaklenec A, Deweerd E. Great expectations: private sector activity in tissue engineering, regenerative medicine, and stem cell therapeutics. Tissue Eng Part A. 2008;14(2):305–315.
Taylor K, Alvarez LR. An Estimate of the Number of Animals Used for Scientific Purposes Worldwide in 2015. Altern Lab Anim. 2019;47(5–6):196–213.
Taylor K, Gordon N, Langley G, Higgins W. Estimates for Worldwide Laboratory Animal Use in 2005. Altern Lab Anim. 2008;36(3):327–342.
Akhtar A. The flaws and human harms of animal experimentation. Camb Q Healthc Ethics. 2015;24(4):407–419.
Sarkiri M, Fox S, Fratila-Apachitei L, Zadpoor A. Bioengineered Skin Intended for Skin Disease Modeling. Int J Mol Sci. 2019;20(1407):1–18.
Robin ED. latroepidemics: A Probe to Examine Systematic Preventable Errors in (Chest) Medicine1-3. American Review of Respiratory Disease. 1987;135(5):1152–1156.
Palmieri PA, Peterson LT, Ford EW. Technological iatrogenesis: New risks force heightened management awareness. J Healthc Risk Manag. 2007;27(4):19–24.
Connell J. Medical tourism: Sea, sun, sand and … surgery. Tourism Management. 2006;27(6):1093–1100.
Connell J. Contemporary medical tourism: Conceptualisation, culture and commodification. Tourism Management. 2013;34:1–13.
Kelley, E. Medical Tourism. World Health Organization (WHO) Patient Safety Programme; 2013.
National Commission on Macroeconomics and Health. Report of the National Commission on Macroeconomics and Health. National Commission on Macroeconomics and Health, Ministry of Health & Family Welfare, Govt. of India; 2005.
Setia A. Freeing Maqāṣid and Maṣlaḥa from Surreptitious Utilitarianism. Islamic Sciences. 2016;14(2):127–157.
Weber D. Medical Hegemony. Int J Complement Alt Med. 2016;3(2):2.