The first Stem Cell-Based Tissue-Engineered Organ Replacement: Implications for Regenerative Medicine and Society
2009; Future Medicine; Volume: 4; Issue: 2 Linguagem: Inglês
10.2217/17460751.4.2.147
ISSN1746-076X
AutoresAnthony P. Hollander, Paolo Macchiarini, Bert Gordijn, Martin Birchall,
Tópico(s)Biomedical Ethics and Regulation
ResumoRegenerative MedicineVol. 4, No. 2 EditorialFree AccessThe first stem cell-based tissue-engineered organ replacement: implications for regenerative medicine and societyAnthony Hollander, Paolo Macchiarini, Bert Gordijn and Martin BirchallAnthony HollanderDepartment of Cellular & Molecular Medicine, University of Bristol, School of Medical Sciences, University Walk, Clifton, Bristol BS8 1TD, UK, Paolo MacchiariniDepartment of General Thoracic Surgery, Hospital Clinic, c Villaroel 170, E-08036 Barcelona, Spain, Bert GordijnEthics Institute, Dublin City University, Glasnevin, Dublin 9, Ireland and Martin Birchall† Author for correspondenceLaryngeal Research Group, UCL Ear Institute, University College London and the Royal National Throat Nose and Ear Hospital, 332 Gray's Inn Road, London WC2A 8EE, UK. Published Online:25 Mar 2009https://doi.org/10.2217/17460751.4.2.147AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit In June 2008, a young woman with end-stage bronchial disease received a decellularized donor tracheal graft that had been repopulated with autologous cells, many of which (chondrocytes) were derived from mesenchymal stem cells; 6 months later, she is well and actively caring for her two young children. She has no signs of stenosis or rejection and is on no immunosuppressive medication [1]. This success has been hailed as a breakthrough in some quarters, but what are the real implications for regenerative medicine and for society?Total, functional organ replacement has represented an elusive nirvana for surgeons for decades. Clinical allografting has led to new life for millions of recipients, but in exchange, immunosuppressant medication has many side effects, including a reduction in life expectancy of 10 years on average. The possibility of using autologous cells, whether embryonic or adult stem cells or, alternatively, mature cultured cells to repopulate organ grafts has now become a reality. This presents a future in which conventional transplantation will become, if not obsolete, either complimentary or even second choice to customized, tissue-engineered replacements. Whilst the trachea may be viewed as a relatively simple organ, solutions to engineering the muscles and nerves to drive bowel, bladder and larynx replacements are also close to the clinic [2,3]. Never has there been a more exciting time to be involved in surgical science.The experience also has major implications for stem cell biology. The realistic prospect of clinical translation gives new impetus to the myriad of cutting edge groups who aim to generate a deeper understanding of the way in which stem cells of all types interact with the human environment in which they are inserted. By close scrutiny of the biological outcomes of our patient's graft and of those implanted in her successors, hypotheses of true clinical relevance may be generated and tested to feedback into the clinic. Thus, the modus operandi of the 'human bioreactor' may become clear and harnessed for technological refinements to the transplant process.This first stem cell-based tissue-engineered organ replacement was still based on a donor tracheal graft. Nevertheless, the clinical success might be an important step to a future practice of fully tissue-engineered organ replacements not depending on donor grafts anymore. The implications of such a practice for society would be twofold.First, such a practice might provide solutions for many of the problems of conventional organ transplantation. In the last few decades enormous progress has been made in the field of conventional transplantation. This has led to an enormous increase in the demand for transplantable organs. However, the supply of transplantable organs has not grown with the same speed [101]. The shortage of donor tissue and organs is becoming more and more acute with each passing year. This poses a huge problem to patients, the transplantation community and society as a whole. In addition, conventional organ transplantation has triggered a lot of difficult ethical problems. For example, there are issues around the definition of human death, questions about our obligation to donate organs and problems of distributive justice. Clearly, a successful practice of fully tissue-engineered organ replacements might more effectively deal with the problem of organ and tissue shortage and would not pose the same ethical problems.Second, populations are aging, not only in the West but worldwide. At first sight, this seems to be a good thing. Aging populations, however, show an increasing incidence of damaged and lost tissues and organs. This problem can be considered as one of our biggest future health challenges. Tissue-engineered organ replacements would be a highly valuable asset in tackling this problem. However, there are still important open questions.Our successful use of decellularized cadaver tracheal tissue as the scaffold for our tissue engineering raises some fundamentally important questions: Did the donor scaffold contribute only shape or did it also contribute functional proteins such as sequestered growth and angiogenic factors? Did the micro- and nano-scale organization of the decellularized trachea play a role in the tissue-engineering process? If the scaffold did indeed supply rather more than a macro-scale template, then we must ask if it will ever be possible to engineer a scaffold from synthetic materials or natural molecules that can play the same role. If we cannot reproduce the sophistication of the natural material in an artificial scaffold then we may have to rely on cadaver material for the foreseeable future.Success for this one recipient has also led to unintended spin-offs for the public perception of stem cell science, and for the ethical framework within which translational scientists and clinicians work. The positive publicity that surrounded this experience permitted the difference between adult and embryonic stem cells to be understood by a wide audience, whilst the debate in internet chat rooms between those for and against embryonic stem cell applications became slightly less based on fear and preconception and slightly more on the evidential base. The courage and perseverance required to battle through the regulatory and clinical barriers to performing such innovative surgery may also pay-off by encouraging other groups hovering on the brink of tissue-engineered organ replacements to step over the threshold. Furthermore, it may assist their respective regulators and funding bodies to look at their plans in a more positive way. Thus, a cohort of such technologies may appear in a shorter space of time than might otherwise have been the case.For the broad field of regenerative medicine, the sights have been raised; raised from the bench-tops to the faces of the patients in the clinic next door. There remains a necessary, but comfortable, home in cell biology and early-phase animal experimentation for stem cell science, but from somewhere funding and regulatory support needs to be found to help others negotiate the overgrown path between the two arenas, via preclinical studies and scale-up/automation facilities. Those countries that have seen this reality early may steal a march on other nations who rest on their laboratory laurels. President Obama's position on stem cell treatments is likely to permit the USA to gear up in this field [102]. However, such competition is healthy and if it helps to generate appropriately commercialized functional tissue-engineered organ replacements to clinics more quickly, then it is the patients who will benefit the most.Meanwhile, for one young woman from Colombia and her children, the implications of the first stem cell-based organ transplant are quite clear.Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.Bibliography1 Macchiarini P, Jungebluth P, Go T et al.: Clinical transplantation of a tissue-engineered airway. Lancet372(9655),2023–2030 (2008).Crossref, Medline, Google Scholar2 Bian W, Bursac N: Engineered skeletal muscle tissue networks with controllable architecture. Biomaterials30(7),1401–1412 (2009).Crossref, Medline, CAS, Google Scholar3 Day RM: Epithelial stem cells and tissue engineered intestine. Curr. Stem Cell Res. Ther.1(1),113–120 (2006).Crossref, Medline, CAS, Google Scholar101 BBC News. Donors up but organs still short. http://news.bbc.co.uk/1/hi/health/7842331.stmGoogle Scholar102 Wall Street Journal, 23rd January 2009. http://online.wsj.com/article/SB123268485825709415.htmlGoogle ScholarFiguresReferencesRelatedDetailsCited ByOral biosciences: The annual review 2022Journal of Oral Biosciences, Vol. 65, No. 1Hydrogel based tissue engineering and its future applications in personalized disease modeling and regenerative therapy4 January 2022 | Beni-Suef University Journal of Basic and Applied Sciences, Vol. 11, No. 1Effect on Cellular Vitality In Vitro of Novel APRF-Chlorhexidine Treated Membranes7 November 2022 | Journal of Functional Biomaterials, Vol. 13, No. 4Effectiveness of platelet rich fibrin alone or in combination with bone grafts in the treatment of infrabony defects: Systematic review and metanalysisHealth Sciences Review, Vol. 5Exosome odyssey to original line in dental regenerationJournal of Oral Biosciences, Vol. 64, No. 3Role of Biomaterials Used for Periodontal Tissue Regeneration—A Concise Evidence-Based Review27 July 2022 | Polymers, Vol. 14, No. 15Platelet rich fibrin versus ozone gel for periodontal regeneration in induced rats' intrabony three-wall periodontal defectsJournal of Oral Biology and Craniofacial Research, Vol. 10, No. 4Introduction: Inception, evolution and future of 3D bioprintingThe Wnt5a Receptor, Receptor Tyrosine Kinase-Like Orphan Receptor 2, Is a Predictive Cell Surface Marker of Human Mesenchymal Stem Cells with an Enhanced Capacity for Chondrogenic Differentiation30 August 2017 | Stem Cells, Vol. 35, No. 11Skin Tissue Engineering16 August 2017Uses of Platelet Rich Fibrin in Regenerative Dentistry: An Overview25 August 2017Use of platelet-rich fibrin in regenerative dentistry: a systematic review27 May 2017 | Clinical Oral Investigations, Vol. 21, No. 6Repopulation of Cirrhotic Liver by Hepatic Stem/Progenitor CellsRevealing cytokine-induced changes in the extracellular matrix with secondary ion mass spectrometryActa Biomaterialia, Vol. 14Tissue Engineering and Regenerative Medicine: Semantic Considerations for an Evolving Paradigm12 January 2015 | Frontiers in Bioengineering and Biotechnology, Vol. 2Repopulation of decellularized whole organ scaffold using stem cells: an emerging technology for the development of neo-organ17 July 2014 | Journal of Artificial Organs, Vol. 17, No. 4Stem cell-based organ replacements—Airway and lung tissue engineeringSeminars in Pediatric Surgery, Vol. 23, No. 3One organ at a time19 February 2014 | EMBO reports, Vol. 15, No. 3Transdifferentiation of Adipose-Derived Stem Cells into Keratinocyte-Like Cells: Engineering a Stratified Epidermis2 December 2013 | PLoS ONE, Vol. 8, No. 12From Fat to SkinPlastic and Reconstructive Surgery, Vol. 132Platelet-Rich Fibrin Promotes Periodontal Regeneration and Enhances Alveolar Bone AugmentationBioMed Research International, Vol. 2013Regeneration and bioengineering of transplantable abdominal organs: current status and future challenges31 October 2012 | Expert Opinion on Biological Therapy, Vol. 13, No. 1Cell therapies and regenerative medicine ‐ the dawn of a new age or more hype than hope?3 July 2012 | Clinical and Translational Medicine, Vol. 1, No. 1Regenerative Medicine as Applied to General SurgeryAnnals of Surgery, Vol. 255, No. 5Architectural and Surface Modification of Nanofibrous Scaffolds for Tissue Engineering15 February 2012Regenerative medicine as applied to solid organ transplantation: current status and future challenges10 November 2010 | Transplant International, Vol. 24, No. 3Human endothelial stem/progenitor cells, angiogenic factors and vascular repair15 September 2010 | Journal of The Royal Society Interface, Vol. 7, No. suppl_6 Vol. 4, No. 2 STAY CONNECTED Metrics History Published online 25 March 2009 Published in print March 2009 Information© Future Medicine LtdFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download
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