Salih Fehmi KATIRCIOĞLU, Hasan Attila KESKİN

Ksenotransplantasyon

Gözden geçirmenin amacı: Bu çalışmanın amacı, ksenotransplantasyondaki son ilerlemeyi vurgulamak ve sağlık sisteminin bir klinik deneyi onaylaması olası hale gelmeden önce kalan engelleri/adımları tartışmaktır. Bulgular: Klinik öncesi modellerde yaşamı destekleyen ksenogreftlerin uzun süreli hayatta kalması, ksenotransplantasyonun klinik deneylerinin tartışılmasına yol açmıştır. FDA onayına dayalı klinik kardiyak ksenotransplant raporları ve beyin ölümü gerçekleşmiş insanlara renal ksenotransplantlar, klinik denemelerin daha fazla değerlendirilmesine yol açmıştır. Transplant topluluğu ve bilim kurulları arasındaki tartışmalar, ksenotransplantların klinik bir denemesinin onaylanmasından önce kritik sonraki adımları belirledi. Bu adımlar, klinik bağışıklık bastırma protokolünün ve genetiği değiştirilmiş bir kaynak hayvandan alınan organın, en az 6 aylık tekrarlanabilir hayatta kalma süresine sahip insan olmayan primatlarda test edilmesini içerir. Ek olarak, uygun viral sürveyans protokolleri ve ksenogreftlerin uygun insan fizyolojisini desteklediğine dair onay, muhtemelen sağlık örgütü onayı için kritik unsurlar olacaktır. Son olarak, insan ölü modelinde yapılacak daha ileri çalışmaların, ksenogreftlere karşı insan immün ve fizyolojik tepkileri hakkında kritik bilgiler sağlaması muhtemeldir. Sonuç: Bu gözden geçirme, insan dışı hayvan modellerindeki mevcut ilerlemeyi ve insan ksenotransplantasyonuna ilişkin son çalışmaları vurgulamaktadır. Ayrıca, klinik bir ksenotransplantasyon denemesi onaylanmadan önce ulaşılması gereken kalan engelleri ve şu anda anlaşılan klinik gerekliliklerini gerekliliklerini de açıklamaktadır.

Anahtar Kelimeler:

Ksenotransplantasyon, renal transplantasyon, kardiyak transplantasyon

PDF

___

1) Dooldeniya MD, Warrens AN. “Xenotransplantation: where are we today?”. Journal of the Royal Society of Medicine. 2003;96 (3): 111–117.
2) Mitchell CB . “Xenotransplanation and Transgenics: The Need to Discuss Limits”. Cbhd. CBHD 2000. Retrieved 19 November 2018. Xenotransplantation. Definition by the World Health Organization.
3) Sarah T, Jason SR. “”Hybrids and Chimeras: A Consultation on the Ethical and Social Implications of Creating Human/Animal Embryos in Research” (2007), by the HFEA”. The Embryo Project at Arizona State University.
4) Tentler JJ, Tan AC, Weekes CD, Jimeno A, Leong S, Pitts TM, Arcaroli JJ, Messersmith WA, Eckhardt SG. “Patient-derived tumour xenografts as models for oncology drug development”. Nature Reviews. Clinical Oncology. 2012; 9 (6): 338–50.
5) Kress JM. “Xenotransplantation: Ethics and economics”. Food and Drug Law Journal. 1998; 53 (2): 353–384. PMID 10346691.
6) Hoffman J, Valencak TG . “A short life on the farm: aging and longevity in agricultural, large-bodied mammals”. GeroScience. 2020; 42 (3): 909–922.
7) “Organ Transplants from Animals: Examining the Possibilities”. Fda.gov. Internet Archive. Archived from the original on December 10, 2007. Retrieved May 21, 2022.
8) Li KYC . “Bioprosthetic Heart Valves: Upgrading a 50-Year Old Technology”. Front Cardiovasc Med. 2019;6:47.
9) Reemtsma, K . “Xenotransplantation: A Historical Perspective”. ILAR Journal. 1995;37 (1): 9–12.
10) Cooper DK. “A brief history of cross-species organ transplantation”. Proceedings (Baylor University. Medical Center). 2012 25 (1): 49–57.
11) Bailey LL, Nehlsen-Cannarella SL, Concepcion W, Jolley WB. “Baboon- to-human cardiac xenotransplantation in a neonate”. JAMA: The Journal of the American Medical Association. 1985;254 (23): 3321–3329.
12) SCMP Reporter (15 Feb 1997). “The heart of darkness”. South China Morning Post.
13) Banerjee R. (15 Jan 1997) “Pig heart transplant: Not many are buying the Assam doctor’s story yet”.. India Today. Retrieved May 21, 2022.
14) Maharashtra Herald, (11 Jan 1997, page 5.)
15) Ruth Mathewson (16 Feb 1997). “Transplant surgeon to lose licence”. South China Morning Post.
16) “Why the US Pig Heart Transplant Was Different From the 1997 Assam Doc’s Surgery”. The Wire Science. January 13, 2022. Retrieved May 21, 2022.
17) M. Gnanapragasam (16–19 Jan 1997). “Perspectives in Medical Ethics”. Bioethics in India: Proceedings of the International Bioethics Workshop in Madras: Biomanagement of Biogeoresources. University of Madras.
18) Rahul Karmakar (January 13, 2022). “A pig heart transplant in Assam in 1997”. The Hindu. Retrieved May 21, 2022.
19) “The Infamous Cardiac Surgeon - Dr Dhani Ram Baruah, All You Need To Know”. The Sentinel (Guwahati). October 23, 2021. Retrieved May 21, 2022.
20) Agarwala, Tora (January 14, 2022). “After pig’s heart transplant in the US, controversial Assam doctor points out had done historic surgery 24 years ago”. The Indian Express. Retrieved May 21, 2022.
21) “Progress in Xenotransplantation Opens Door to New Supply of Critically Needed Organs”. NYU Langone News. Retrieved May 21, 2022.
22) Weintraub, Karen (October 19, 2021). “Pig Kidneys to the Rescue? Groundbreaking Transplant a Step Toward Solving our Organ Shortage”. USA Today. Retrieved September 11, 2022.
23) Kotz, Deborah (January 10, 2022). “University of Maryland School of Medicine Faculty Scientists and Clinicians Perform Historic First Successful Transplant of Porcine Heart into Adult Human with End-Stage Heart Disease”. University of Maryland School of Medicine. Retrieved May 21, 2022.
24) “Man gets genetically-modified pig heart in world-first transplant”. BBC News. January 11, 2022. Retrieved May 21, 2022.
25) Neergaard, Lauran; Johnson, Carla K. (March 9, 2022). “US man who got 1st pig heart transplant dies after 2 months”. Associated Press. Retrieved May 21, 2022.
26) DeVries, Colin (July 12, 2022). “Successful Heart Xenotransplant Experiments at NYU Langone Set Protocol for Pig-to-Human Organ Transplants”. NYU Langone Health. Retrieved September 11, 2022.
27) Molteni, Megan (January 20, 2022). “After a Flurry of Firsts, Xenotransplantation is Suddenly Back in the Spotlight”. Stat News. Retrieved September 11, 2022.
28) Healy DG, Lawler Z, McEvoy O, Parlon B, Baktiari N, Egan JJ, Hurley J, McCarthy JF, Mahon N, Wood AE. “Heart transplant candidates: Factors influencing waiting list mortality”. Irish Medical Journal. 2005;98 (10): 235–237. PMID 16445141.
29) David H S. “Transplantation Tolerance Through Mixed Chimerism: From Allo to Xeno”. Xenotransplantation. 2018;25 (3): e12420.
30) Platt JL, Cascalho M. “New and old technologies for organ replacement”. Current Opinion in Organ Transplantation. 2013;18 (2): 179–85.
31) Van Der Windt DJ., Bottino R, Kumar G, Wijkstrom M, Hara H, Ezzelarab M, Ekser B, Phelps C, Murase N, Casu A, Ayares D, Lakkis FG, Trucco M, Cooper DK.”Clinical islet xenotransplantation: How close are we?”. Diabetes. 2012;61 (12): 3046–55.
32) Tisato V, Cozzi E . “Xenotransplantation: An Overview of the Field”. Xenotransplantation. Methods in Molecular Biology. 2012;Vol. 885. pp. 1–16.
33) Richmond A, Su Y. “Mouse xenograft models vs GEM models for human cancer therapeutics”. Disease Models and Mechanisms. 2008;1 (2– 3): 78–82.
34) JAX® In Vivo Xenograft Services. JAX® NOTES Issue 508, Winter 2008.
35) Lewis, Tanya (2015-01-21). “Growing human kidneys in rats sparks ethical debate”. CBS News. Retrieved 2015-09-26.
36) Michler R. “Xenotransplantation: Risks, Clinical Potential, and Future Prospects”. Emerging Infectious Diseases. 1996;2(1): 64–70.
37) Kemter E, DennerJ, Wolf E.”Will Genetic Engineering Carry Xenotransplantation of Pig Islets to the Clinic?”. Current Diabetes Reports. 2018;18(11):103.
38) Taylor, L. (2007). Xenotransplantation. Emedicine.com
39) Cooper D, Ekser B, Ramsoondar J, Phelps C, Ayares D. “The role of genetically engineered pigs in xenotransplantation research”. The Journal of Pathology. 2015;238 (2): 288–299.
40) Reiss, MJ. “The Ethics of Xenotransplantation”. Journal of Applied Philosophy. 2000;17(3):253–262.
41) Dolgin E. “First GM pigs for allergies. Could xenotransplants be next?”. Nature Biotechnology. 2021;39(4):397–400.
42) Matsunari H, Nagashima H, Watanabe M et al. Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs”. PNAS. 2013;110(12):4557–4562.
43) Boneva RS, Folks TM, Chapman LE . “Infectious disease issues in xenotransplantation”. Clinical Microbiology Reviews. 2001;14(1):1–14.
44) Candinas D, Adams DH. “Xenotransplantation: Postponed by a millennium?”. QJM. 2000;93 (2): 63–66.
45) Latemple DC, Galili U. “Adult and neonatal anti-Gal response in 47 knock-out mice for alpha1,3galactosyltransferase”. Xenotransplantation. 1998;5(3): 191–196.
46) Sharma A, Okabe J, Birch P, McClellan SB, Martin MJ, Platt JL, Logan JS. “Reduction in the level of Gal(alpha1,3)Gal in transgenic mice and pigs by the expression of an alpha(1,2)fucosyltransferase”. Proceedings of the National Academy of Sciences of the United States of America. 1996;93 (14): 7190–7195.
47) Huang J, Gou D, Zhen C, Jiang D, Mao X, Li W, Chen S, Cai C. “Protection of xenogeneic cells from human complement-mediated lysis by the expression of human DAF, CD59 and MCP”. FEMS Immunology and Medical Microbiology.2001;31(3):203–209.
48) Takahashi T, Saadi S, Platt JL. “Recent advances in the immunology of xenotransplantation”. Immunologic Research. 1997;16(3): 273–297.
49) Abbas A, Lichtman A. Cellular and Molecular Immunology, 5th ed.,2005; pp. 81, 330–333, 381, 386. Elsevier Saunders, Pennsylvania,ISBN 0-7216- 0008-5.
50) Vanderpool HY. “Xenotransplantation: Progress and promise”. BMJ.1999;319(7220): 1311.
51) Cowan PJ, Robson SC. “Controlling coagulation dysregulation in xenotransplantation”. Current Opinion in Organ Transplantation. 2011;16(2):214– 21.
52) Ekser B, Cooper DK. “Overcoming the barriers to xenotransplantation: prospects for the future”. Expert Review of Clinical Immunology. 2011;6(2):219–30.
53) Beigel J, Farrar J, Han A, Hayden F, Hyer R, De Jong M, Lochindarat S, Nguyen T, Nguyen T, Tran TH, Nicoll A, Touch S, Yuen K Y. Writing Committee of the World Health Organization (WHO) Consultation on Human Influenza A/H5 (2005).
54) Beigel JG, et al. “Avian Influenza A (H5N1) Infection in Humans”. New England Journal of Medicine. 2005;353(13):1374–1385.
55) )Takeuchi Y, Weiss R A. “Xenotransplantation: Reappraising the risk of retroviral zoonosis”. Current Opinion in Immunology. 2000;12(5): 504–507.
56) FDA. (2006) Xenotransplantation Action Plan: FDA Approach to the Regulation of Xenotransplantation. Center for Biologics Evaluation and Research.
57) “The Australian National Health and Medical Research Council’s 2005 statement on xenotransplantation” (PDF). Archived from the original (PDF) on 2008-07-22. Retrieved 2008-11-06.
58) Dean, Tim (December 10, 2009). “Xenotransplantation ban lifted in Australia”. Life Scientist. Archived from the original on 2009-12-15. Retrieved May 21, 2022.
59) Armstrong JA, Porterfield JS, De Madrid AT. “C-type virus particles in pig kidney cell lines”. The Journal of General Virology. 1971; (2): 195–198.
60) Patience C, Takeuchi Y, Weiss RA. “Infection of human cells by an endogenous retrovirus of pigs”. Nature Medicine. 1997;3 (3): 282–286.
61) Rogel-Gaillard C, Bourgeaux N, Billault A, Vaiman M, Chardon P. “Construction of a swine BAC library: Application to the characterization and mapping of porcine type C endoviral elements”. Cytogenetics and Cell Genetics. 1999;5(3–4):205–211.
62) Takeuchi Y, Patience C, Magre S, Weiss RA, Banerjee PT, Le Tissier P, Stoye JP. “Host range and interference studies of three classes of pig endogenous retrovirus”. Journal of Virology. 1998;72 (12): 9986–9991.
63) “Xenotransplantation: How Pig Organs Could Be Transplanted into Humans”. Animal Biotech Industries. March 19, 2018. Archived from the original on 2018-11-06. Retrieved November 5, 2018.
64) Zimmerman, Carl (Oct 15, 2015). “Editing of Pig DNA May Lead to More Organs for People”. The New York Times.
65) Weisman, Robert (March 16, 2017). “Startup eGenesis pushes toward goal: transplanting pig organs into humans”. The Boston Globe.
66) PETA Media Center: Factsheet: Xenotransplantation Archived June 26, 2010, at the Wayback Machine. Peta.org. Retrieved on 2013-10-17.
67) Sharp, Leslie (2013). The Transplant Imaginary Mechanical Hearts, Animal Parts, and Moral Thinking in Highly Experimental Science. University of California Press. p. 38. ISBN 9780520277960.
68) Cooper David K C, Groth CG, McKenzie Ian FC, Goldman E, Fano A, Vanderpool HY. Xenotransplantation”. BMJ: British Medical Journal. 2000;320 (7238): 868–869.
69) Rothblatt, Martine (2004). Your Life or Mine. Burlington, VT: Ashgate Publishing Company. pp. 109–110. ISBN 978-0754623915.
70) Von Derdidas, Ihrwir (2009) A More Modest Proposal Archived July 12, 2011, at the Wayback Machine. Hotel St. George Press.
71) Rémy C. “The Animal Issue in Xenotransplantation: Controversies in France and the United States”. History and Philosophy of the Life Sciences. 2009;31(3):405–428.
72) Anderson M. “Xenotransplantation: A Bioethical Evaluation”. Journal of Medical Ethics. 2006;32(4): 205–208.
73) Ellison T. “Xenotransplantation—ethics and regulation”. Xenotransplantation. 2006;13 (6): 505–9.
74) Kaiser M. “Xenotransplantation—ethical considerations based on human and societal perspectives”. Acta Veterinaria Scandinavica. Supplementum. 2004;99: 65–73. PMID 15347151.
75) Sykes M, D’Apice A, Sandrin M. “Position Paper of the Ethics Committee of the International Xenotransplantation Association”. Xenotransplantation. 2003;10(3):194–203.
76) Sharp, Leslie (2013). The Transplant Imaginary Mechanical Hearts, Animal Parts, and Moral Thinking in Highly Experimental Science. University of California Press. p. 45. ISBN 9780520277960.
77) Florencio PS, Ramanathan ED. “Are Xenotransplantation Safeguards Legally Viable?”. Berkeley Technology Law Journal. 2001;16:945. JSTOR 24116896. PMID 15212014. Retrieved May 21, 2022.
78) United States Food and Drug Administration. Guidance for Industry: Source Animal, Product, Preclinical, and Clinical Issues Concerning the Use of XTx Products in Humans. Washington, DC: US FDA, 2001.
79) Reichart B, Cooper DKC, Längin M, Tönjes RR, Pierson RN, Wolf E. Cardiac xenotransplantation: from concept to clinic. Cardiovasc Res. 2023 Feb 3;118(18):3499-3516.
80) Sugimoto S, Kobayashi E, Kanai T, Sato T. In Vivo Intestinal Research Using Organoid Transplantation.. Keio J Med. 2022 Dec 25;71(4):73-81.
81) Anwar IJ, DeLaura I, Ladowski J, Gao Q, Knechtle SJ, Kwun J. Complement- targeted therapies in kidney transplantation-insights from preclinical studies. Front Immunol. 2022 Oct 13;13:984090.
82) Shahab M, Din NU, Shahab N. Cureus. Genetically Engineered Porcine Organs for Human Xenotransplantation. 2022 Sep 12;14(9):e29089.
83) Sykes M, Sachs DH. Progress in xenotransplantation: overcoming immune barriers. Nat Rev Nephrol. 2022 Dec;18(12):745-761.
84) Denner J. Virus Safety of Xenotransplantation. Denner J. Viruses. 2022 Aug 30;14(9):1926.
85) Mueller NJ, Denner J. Porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV): A threat for xenotransplantation? Xenotransplantation. 2022 Sep;29(5):e12775.
86) Kano M, Mizutani E, Homma S, Masaki H, Nakauchi H. Xenotransplantation and interspecies organogenesis: current status and issues.Front Endocrinol (Lausanne). 2022 Aug 5;13:963282.
87) Zhou Q, Li T, Wang K, Zhang Q, Geng Z, Deng S, Cheng C, Wang Y. Current status of xenotransplantation research and the strategies for preventing xenograft rejection. Front Immunol. 2022 Jul 28;13:928173.
88) Boulet J, Cunningham JW, Mehra MR Cardiac Xenotransplantation: Challenges, Evolution, and Advances. JACC Basic Transl Sci. 2022 Jun 15;7(7):716-729.
89) Greising SM, Weiner JI, Garry DJ, Sachs DH, Garry MG. Human muscle in gene edited pigs for treatment of volumetric muscle loss. Front Genet. 2022 Jul 25;13:948496.
90) Carrier AN, Verma A, Mohiuddin M, Pascual M, Muller YD, Longchamp A, Bhati C, Buhler LH, Maluf DG, Meier RPH. Xenotransplantation: A New Era. Front Immunol. 2022 Jun 9;13:900594.
91) Fischer K, Schnieke A. Xenotransplantation becoming reality. Transgenic Res. 2022 Jun;31(3):391-398.
92) Mou L, Shi G, Cooper DKC, Lu Y, Chen J, Zhu S, Deng J, Huang Y, Ni Y, Zhan Y, Cai Z, Pu Z. Current Topics of Relevance to the Xenotransplantation of Free Pig Islets. Front Immunol. 2022 Apr 1;13:854883.
93) Singh AK, Goerlich CE, Shah AM, Zhang T, Tatarov I, Ayares D, Horvath KA, Mohiuddin MM. Cardiac Xenotransplantation: Progress in Preclinical Models and Prospects for Clinical Translation. Transpl Int. 2022 Mar 23;35:10171.