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Moving the Margins: Updates on the Renaissance in Machine Perfusion for Organ Transplantation

  • Tissue Engineering and Regeneration (J. Wertheim, Section Editor)
  • Published:
Current Transplantation Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Escalating end-organ disease coupled with stagnant donor pools has begotten global organ shortages. Ex vivo organ perfusion, used briefly in the early days of clinical transplant and then sidelined for decades by static cold storage, has resurged to address this organ paucity. Given the recent prolific application of machine perfusion as a platform for assessment, preservation, and treatment of marginal grafts, this review summarizes salient results from the past 2–3 years in kidney, liver, lung, heart, pancreas, vascularized composite allograft, and xenograft transplantation.

Recent Findings

Clinical trials have established the ability of ex vivo perfusion to make previously declined thoracic and abdominal organs transplantable without sacrificing short- or long-term function and survival. In addition to extended assessment and superior preservation, machine perfusion enables targeted delivery of cutting-edge gene and immunomodulatory therapies. At the leading edge, ex vivo perfusion has recently led to breakthroughs in xenotransplantation, enabled ischemia-free liver transplants, and been incorporated into out-of-hospital organ resuscitation centers.

Summary

Ex vivo machine perfusion is transitioning from being dormant to indispensable in clinical organ transplantation. Providing a platform for extended assessment, superior preservation, and targeted therapy, ex vivo organ perfusion can make marginal, previously declined organs a part of the donor pool. Pioneering pre-clinical studies continue to provide guidance on how to optimize and leverage this invaluable system for further expansion of lifesaving organ transplantation.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Carrel A, Lindbergh CA. The culture of whole organs. Science. 1935;81(80):621–3.

    Article  CAS  PubMed  Google Scholar 

  2. Dutkowski P, Guarrera JV, de Jonge J, Martins PN, Porte RJ, Clavien PA. Evolving trends in machine perfusion for liver transplantation. Gastroenterology. 2019;156(6):1542–7. https://doi.org/10.1053/j.gastro.2018.12.037.

    Article  PubMed  Google Scholar 

  3. Karimian N, Yeh H. Opportunities for therapeutic intervention during machine perfusion. Curr Transplant Rep. 2017;4(2):141–8. https://doi.org/10.1007/s40472-017-0144-y.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Belzer FO, Ashby BS, Gulyassy PF, Powell M. Successful seventeen-hour preservation and transplantation of human-cadaver kidney. N Engl J Med. 1968;278(11):608–10.

    Article  CAS  PubMed  Google Scholar 

  5. Moers C, Smits J, Maathuis M, Treckmann J, van Gelder F, Napieralski B. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med. 2009;360(1):609–19. https://doi.org/10.1056/NEJMoa1109071.

    Article  CAS  Google Scholar 

  6. Jochmans I, Hofker H, Davies L, Knight S, Pirenne J, Ploeg R. Oxygenated hypothermic machine perfusion of kidneys donated after circulatory death: an international randomised controlled trial [abstract]. In: American Journal of Transplantation. ; 2019:19 (suppl 3). https://atcmeetingabstracts.com/abstract/oxygenated-hypothermic-machine-perfusion- of-kidneys-donated-after-circulatory-death-an-international-randomised-controlled- trial/. Accessed 12 Oct 2019

  7. Bhattacharjee RN, Ruthirakanthan A, Sun Q, Richard-Mohamed M, Luke S, Jiang L, et al. Subnormothermic oxygenated perfusion optimally preserves donor kidneys ex vivo. Kidney Int Rep. 2019;4(9):1323–33. https://doi.org/10.1016/j.ekir.2019.05.013.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Bhattacharjee RN, Patel SVB, Sun Q, et al. Renal protection against ischemia perfusion injury- hemoglobin based oxygen carrier-201 vs. blood as an oxygen carrier in ex vivo subnormothermic machine perfusion. Transplantation. 2019. https://doi.org/10.1097/TP.0000000000002967.

  9. Aburawi MM, Fontan FM, Karimian N, et al. Synthetic hemoglobin-based oxygen carriers are an acceptable alternative for packed red blood cells in normothermic kidney perfusion. Am J Transplant. 2019;(February):2814–24. https://doi.org/10.1111/ajt.15375.

  10. •• Hosgood SA, Thompson E, Moore T, Wilson CH, Nicholson ML. Normothermic machine perfusion for the assessment and transplantation of declined human kidneys from donation after circulatory death donors. Br J Surg. 2018;105(4):388–94. https://doi.org/10.1002/bjs.10733The first report of transplanting declined kidneys after normothermic perfusion for assessment.

    Article  CAS  PubMed  Google Scholar 

  11. Georgiades F, Hosgood SA, Butler AJ, Nicholson ML. Use of ex vivo normothermic machine perfusion after normothermic regional perfusion to salvage a poorly perfused DCD kidney. Am J Transplant. 2019;(July):1–5. https://doi.org/10.1111/ajt.15547.

  12. Hosgood SA, Nicholson ML. An assessment of urinary biomarkers in a series of declined human kidneys measured during ex vivo normothermic kidney perfusion. Transplantation. 2017;101(9):2120–5. https://doi.org/10.1097/TP.0000000000001504.

    Article  CAS  PubMed  Google Scholar 

  13. Woud WW, Merino A, Hoogduijn MJ, et al. Nanoparticle release by extended criteria donor kidneys during normothermic machine perfusion. Transplantation. 2019;103(5):e110–1. https://doi.org/10.1097/TP.0000000000002642.

    Article  PubMed  Google Scholar 

  14. Hosgood SA, Saeb-Parsy K, Wilson C, Callaghan C, Collett D, Nicholson ML. Protocol of a randomised controlled, open-label trial of ex vivo normothermic perfusion versus static cold storage in donation after circulatory death renal transplantation. BMJ Open. 2017;7(1):1–7. https://doi.org/10.1136/bmjopen-2016-012237.

    Article  Google Scholar 

  15. Kaths JM, Echeverri J, Chun YM, Cen JY, Goldaracena N, Linares I, et al. Continuous normothermic ex vivo kidney perfusion improves graft function in donation after circulatory death pig kidney transplantation. Transplantation. 2017;101(4):754–63. https://doi.org/10.1097/TP.0000000000001343.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kaths JM, Cen JY, Chun YM, Echeverri J, Linares I, Ganesh S, et al. Continuous normothermic ex vivo kidney perfusion is superior to brief normothermic perfusion following static cold storage in donation after circulatory death pig kidney transplantation. Am J Transplant. 2017;17(4):957–69. https://doi.org/10.1111/ajt.14059.

    Article  CAS  PubMed  Google Scholar 

  17. Kaths JM, Echeverri J, Linares I, Cen JY, Ganesh S, Hamar M, et al. Normothermic ex vivo kidney perfusion following static cold storage—brief, intermediate, or prolonged perfusion for optimal renal graft reconditioning? Am J Transplant. 2017;17(10):2580–90. https://doi.org/10.1111/ajt.14294.

    Article  CAS  PubMed  Google Scholar 

  18. Kaths JM, Hamar M, Echeverri J, et al. Normothermic ex vivo kidney perfusion for graft quality assessment prior to transplantation. Am J Transplant. 2018;18(3):580–9. https://doi.org/10.1111/ajt.14491.

    Article  CAS  PubMed  Google Scholar 

  19. Hamar M, Urbanellis P, Kaths MJ, Kollmann D, Linares I, Ganesh S, et al. Normothermic ex vivo kidney perfusion reduces warm ischemic injury of porcine kidney grafts retrieved after circulatory death. Transplantation. 2018;102(8):1262–70. https://doi.org/10.1097/TP.0000000000002245.

    Article  PubMed  Google Scholar 

  20. von Horn C, Minor T. Improved approach for normothermic machine perfusion of cold stored kidney grafts. Am J Transl Res. 2018;10(6):1921–9.

    Google Scholar 

  21. Brasile L, Henry N, Orlando G, Stubenitsky B. Potentiating renal regeneration using mesenchymal stem cells. Transplantation. 2019;103(2):307–13. https://doi.org/10.1097/TP.0000000000002455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Thompson E, Bates L, Ibrahim IK, et al. Novel delivery of cellular therapy to reduce ischaemia reperfusion injury in kidney transplantation [pre peer-review]. medRxiv. 2019:1–34. https://doi.org/10.1101/19005546.

  23. Tietjen GT, Hosgood SA, DiRito J, et al. Nanoparticle targeting to the endothelium during normothermic machine perfusion of human kidneys. Sci Transl Med. 2017;9(418). https://doi.org/10.1126/scitranslmed.aam6764.

  24. DiRito JR, Hosgood SA, Tietjen GT, Nicholson ML. The future of marginal kidney repair in the context of normothermic machine perfusion. Am J Transplant. 2018;18(10):2400–8. https://doi.org/10.1111/ajt.14963.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Miñambres E, Suberviola B, Dominguez-Gil B, Rodrigo E, Ruiz-San Millan JC, Rodríguez-San Juan JC, et al. Improving the outcomes of organs obtained from controlled donation after circulatory death donors using abdominal Normothermic regional perfusion. Am J Transplant. 2017;17(8):2165–72. https://doi.org/10.1111/ajt.14214.

    Article  PubMed  Google Scholar 

  26. Antoine C, Savoye E, Gaudez F, et al. Kidney transplant from uncontrolled donation after circulatory death: contribution of normothermic regional perfusion. Transplantation. 2019. https://doi.org/10.1097/tp.0000000000002753.

  27. Guarrera JV, Henry SD, Samstein B, Odeh-Ramadan R, Kinkhabwala M, Goldstein MJ, et al. Hypothermic machine preservation in human liver transplantation: the first clinical series. Am J Transplant. 2010;10(2):372–81. https://doi.org/10.1111/j.1600-6143.2009.02932.x.

    Article  CAS  PubMed  Google Scholar 

  28. Watson CJE, Jochmans I. From “gut feeling” to objectivity: machine preservation of the liver as a tool to assess organ viability. Curr Transplant Rep. 2018;5(1):72–81. https://doi.org/10.1007/s40472-018-0178-9.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Weissenbacher A, Vrakas G, Nasralla D, Ceresa CDL. The future of organ perfusion and re-conditioning. Transpl Int. 2019;32(6):586–97. https://doi.org/10.1111/tri.13441.

    Article  PubMed  Google Scholar 

  30. Schlegel A, Muller X, Kalisvaart M, Muellhaupt B, Perera MTPR, Isaac JR, et al. Outcomes of DCD liver transplantation using organs treated by hypothermic oxygenated perfusion before implantation. J Hepatol. 2019;70(1):50–7. https://doi.org/10.1016/j.jhep.2018.10.005.

    Article  CAS  PubMed  Google Scholar 

  31. van Rijn R, van Leeuwen OB, Matton APM, Burlage LC, Wiersema-Buist J, van den Heuvel M, et al. Hypothermic oxygenated machine perfusion reduces bile duct reperfusion injury after transplantation of donation after circulatory death livers. Liver Transpl. 2018;24(5):655–64. https://doi.org/10.1002/lt.25023.

    Article  PubMed  PubMed Central  Google Scholar 

  32. van Rijn R, Karimian N, Matton APM, Burlage LC, Westerkamp AC, van den Berg A, et al. Dual hypothermic oxygenated machine perfusion in liver transplants donated after circulatory death. Br J Surg. 2017;104(7):907–17. https://doi.org/10.1002/bjs.10515.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Patrono D, Surra A, Catalano G, Rizza G, Berchialla P, Martini S, et al. Hypothermic oxygenated machine perfusion of liver grafts from brain-dead donors. Sci Rep. 2019;9(1):1–14. https://doi.org/10.1038/s41598-019-45843-3.

    Article  CAS  Google Scholar 

  34. Muller X, Schlegel A, Kron P, et al. Novel real-time prediction of liver graft function during hypothermic oxygenated machine perfusion before liver transplantation. Ann Surg. 2019;270(5):1. https://doi.org/10.1097/sla.0000000000003513.

    Article  Google Scholar 

  35. Van Rijn R, Van Den Berg AP, Erdmann JI, et al. Study protocol for a multicenter randomized controlled trial to compare the efficacy of end-ischemic dual hypothermic oxygenated machine perfusion with static cold storage in preventing non-anastomotic biliary strictures after transplantation of liver gra. BMC Gastroenterol. 2019;19(1):1–12. https://doi.org/10.1186/s12876-019-0956-6.

    Article  Google Scholar 

  36. Czigany Z, Schöning W, Ulmer TF, Bednarsch J, Amygdalos I, Cramer T, et al. Hypothermic oxygenated machine perfusion (HOPE) for orthotopic liver transplantation of human liver allografts from extended criteria donors (ECD) in donation after brain death (DBD): a prospective multicentre randomised controlled trial (HOPE ECD-DBD). BMJ Open. 2017;7(10):1–9. https://doi.org/10.1136/bmjopen-2017-017558.

    Article  Google Scholar 

  37. Nasralla D, Coussios CC, Mergental H, et al. A randomized trial of normothermic preservation in liver transplantation * for the consortium for organ preservation in europe. Nature. 2018. https://doi.org/10.1038/s41586-018-0047-9.

  38. Markmann J, Ghobrial M, Magliocca J, Demetris A, Abouljoud M. Results of the initial phase of the portable Organ Care System (OCS™) Liver PROTECT Pivotal Trial [abstract]. Am J Transplant. 2017;17(suppl 3) https://atcmeetingabstracts.com/abstract/results-of-the-initial-phase-of-the-portable-organ-care-system-ocs-liver-protect-pivotal-trial/. Accessed 3 Oct 2019.

  39. • Watson CJE, Kosmoliaptsis V, Pley C, et al. Observations on the ex situ perfusion of livers for transplantation. Am J Transplant. 2018;18(8):2005–20. https://doi.org/10.1111/ajt.14687Largest report of declined livers being transplanted following NMP.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ghinolfi D, Rreka E, De Tata V, et al. Pilot, open, randomized, prospective trial for normothermic machine perfusion evaluation in liver transplantation from older donors. Liver Transpl. 2019;25(3):436–49. https://doi.org/10.1002/lt.25362.

    Article  PubMed  Google Scholar 

  41. Mergental H, Perera MTPR, Laing RW, et al. Transplantation of declined liver allografts following normothermic ex-situ evaluation. Am J Transplant. 2016;16(11):3235–45. https://doi.org/10.1111/ajt.13875.

    Article  CAS  PubMed  Google Scholar 

  42. Ceresa CDL, Nasralla D, Watson CJE, et al. Transient cold storage prior to normothermic liver perfusion may facilitate adoption of a novel technology. Liver Transpl. 2019:1–11. https://doi.org/10.1002/lt.25584.

  43. Afford S, Wallace C, Attard J, Boteon Y, Laing R, Perera T, et al. Viability Testing and Transplantation of Marginal Donor Livers (VITTAL) Trial outcomes: proteomic analysis of perfusates from livers undergoing normothermic machine liver perfusion reveals biomarkers predictive of graft viability and post-transplant compl. Am J Transplant. 2019;19(suppl 3) https://atcmeetingabstracts.com/abstract/viability-testing-and-transplantation-of-marginal-donor-livers-vittal-trial-outcomes-proteomic-analysis-of-perfusates-from-livers-undergoing-normothermic-machine-liver-perfusion-reveals-biomarkers. Accessed 13 Oct 2019

  44. Laing RW, Mergental H, Yap C, Kirkham A, Whilku M, Barton D, et al. Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial. BMJ Open. 2017;7(11):1–15. https://doi.org/10.1136/bmjopen-2017-017733.

    Article  Google Scholar 

  45. Paul A. [ISRCTN15686690] Controlled oxygenated rewarming as adjunct in liver transplantation (CORAL) of human allografts from extended criteria donors (ECD): a prospective randomized controlled trial. ISRCTN Regist. 2017. https://www.cochranelibrary.com/central/doi/10.1002/central/CN-01894285/full. Accessed 16 Oct 2019

  46. He X, Guo Z, Zhao Q, Ju W, Wang D, Wu L, et al. The first case of ischemia-free organ transplantation in humans: a proof of concept. Am J Transplant. 2018;18(3):737–44. https://doi.org/10.1111/ajt.14583.

    Article  PubMed  Google Scholar 

  47. Ju W, Huang S, Guo Z, Chen G, He X. Ischemia-free liver transplantation for fatty liver grafts in human [abstract]. In: American Transplant Congress. 2018. doi:https://doi.org/10.1111/ajt.14918 Accessed 17 Oct 2019

  48. He X, Guo Z, Huang S, et al. The first series of ischemia-free liver transplantation in human [abstract]. In: American Transplant Congress. 2018. https://atcmeetingabstracts.com/abstract/the-?rst-series-of-ischemia-free-liver-transplantation-in-human/. Accessed 17 Oct 2019

  49. Guo Z, He X, Tang Y, et al. Ischemia-free liver transplantation in pigs: ischemia reperfusion injury is avoidable? [abstract]. In: American Transplant Congress. 2018. https://doi.org/10.1111/ajt.14918

  50. He X, Guo Z, Ju W, et al. Improved transplant outcomes in ischemia-free liver transplantation : a report of the first 30 cases [abstract]. In: American Transplant Congress. 2019. https://atcmeetingabstracts.com/abstract/improved-transplant-outcomes-in-ischemia-free-liver-transplantation-a-report-of-the-?rst-30-cases/. Accessed 17 Oct 2019

  51. Yang J, Huang S, Zhang Z, et al. Ischemia-free liver transplantation protects bile duct from ischemia/reperfusion injury [abstract]. In: American Transplant Congress. 2019. https://atcmeetingabstracts.com/abstract/ischemia-free-liver-transplantation-protects-bile-duct-from-ischemia-reperfusion-injury/. Accessed 17 Oct 2019

  52. Wang L, Guo Z, Yang L, et al. Protective effect of ischemic-free liver transplantation technique on distant multiple organ function [abstract]. In: American Transplant Congress. 2019. https://atcmeetingabstracts.com/abstract/protective-effect-of-ischemic-free-liver-transplantation-technique-on-distant-multiple-organ-function/. Accessed 17 Oct 2019

  53. Yoshimoto S, Torai S, Yoshioka M, Nadahara S, Kobayashi E. Continuous resuscitation for porcine liver transplantation from donor after cardiac death. Transplant Proc. 2019;51(5):1463–7. https://doi.org/10.1016/j.transproceed.2019.03.016.

    Article  PubMed  Google Scholar 

  54. van Leeuwen OB, Ubbink R, de Meijer VE, Porte RJ. The first case of ischemia - free organ transplantation in humans : a proof of concept. Am J Transplant. 2018;14869. https://doi.org/10.1111/ajt.14869.

  55. van Leeuwen OB, Fujiyoshi M, Ubbink R, Werner MJM, Brüggenwirth IMA, Porte RJ, et al. Ex situ machine perfusion of human donor livers via the surgically reopened umbilical vein. Transplantation. 2019;103(10):2130–5. https://doi.org/10.1097/tp.0000000000002615.

    Article  PubMed  Google Scholar 

  56. Hessheimer AJ, Coll E, Torres F, Ruíz P, Gastaca M, Rivas JI, et al. Normothermic regional perfusion vs. super-rapid recovery in controlled donation after circulatory death liver transplantation. J Hepatol. 2019;70(4):658–65. https://doi.org/10.1016/j.jhep.2018.12.013.

    Article  PubMed  Google Scholar 

  57. Ruiz P, Gastaca M, Bustamante FJ, Ventoso A, Palomares I, Prieto M, et al. Favorable outcomes after liver transplantation with normothermic regional perfusion from donors after circulatory death: a single-center experience. Transplantation. 2019;103(5):938–43. https://doi.org/10.1097/TP.0000000000002391.

    Article  CAS  PubMed  Google Scholar 

  58. Hagness M, Foss S, Sørensen DW, Syversen T, Bakkan PA, Dahl T, et al. Liver transplant after normothermic regional perfusion from controlled donors after circulatory death: the Norwegian experience. Transplant Proc. 2019;51(2):475–8. https://doi.org/10.1016/j.transproceed.2019.01.066.

    Article  CAS  PubMed  Google Scholar 

  59. Cypel M, Neyrinck A, Machuca TN. Ex vivo perfusion techniques: state of the art and potential applications. Intensive Care Med. 2019;45(3):354–6. https://doi.org/10.1007/s00134-019-05568-3.

    Article  PubMed  Google Scholar 

  60. Possoz J, Neyrinck A, Van Raemdonck D. Ex vivo lung perfusion prior to transplantation: an overview of current clinical practice worldwide. J Thorac Dis. 2019;11(4):1635–50. https://doi.org/10.21037/jtd.2019.04.33.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Steen S, Sjiberg T, Pierre L, Liao Q, Algotsson L. Transplantation of lungs from non-neart-beating donnor. Lancet. 2001;356:825–9.

    Article  Google Scholar 

  62. Cypel M, Yeung JC, Mingyao L, et al. Normothermic ex vivo lung perfusion in clinical lung transplantation. N Engl J Med. 2011;364(15):1431–40. https://doi.org/10.1056/NEJMoa1014597.

    Article  CAS  PubMed  Google Scholar 

  63. Loor G, Warnecke G, Villavicencio MA, et al. Portable normothermic ex-vivo lung perfusion, ventilation, and functional assessment with the Organ Care System on donor lung use for transplantation from extended-criteria donors (EXPAND): a single-arm, pivotal trial. Lancet Respir Med. 2019;2600(19). https://doi.org/10.1016/s2213-2600(19)30200-0.

  64. Schiavon M, Faggi G, Rebusso A, Lunardi F, Comacchio G, di Gregorio G, et al. Extended criteria donor lung reconditioning with the Organ Care System Lung: a single institution experience. Transpl Int. 2019;32(2):131–40. https://doi.org/10.1111/tri.13365.

    Article  PubMed  Google Scholar 

  65. Zhang ZL, van Suylen V, van Zanden JE, van de Wauwer C, Verschuuren EAM, van der bij W, et al. First experience with ex vivo lung perfusion for initially discarded donor lungs in the Netherlands: a single-centre study. Eur J Cardiothorac Surg. 2019;55(5):920–6. https://doi.org/10.1093/ejcts/ezy373.

    Article  PubMed  Google Scholar 

  66. Nilsson T, Wallinder A, Henriksen I, Nilsson JC, Ricksten SE, Møller-Sørensen H, et al. Lung transplantation after ex vivo lung perfusion in two Scandinavian centres. Eur J Cardiothorac Surg. 2019;55(4):766–72. https://doi.org/10.1093/ejcts/ezy354.

    Article  PubMed  Google Scholar 

  67. Koch A, Pizanis N, Olbertz C, Abou-Issa O, Taube C, Slama A, et al. One-year experience with ex vivo lung perfusion: preliminary results from a single center. Int J Artif Organs. 2018;41(8):460–6. https://doi.org/10.1177/0391398818783391.

    Article  PubMed  Google Scholar 

  68. Divithotawela C, Cypel M, Martinu T, et al. Long-term outcomes of lung transplant with ex vivo lung perfusion. JAMA Surg. 2019. https://doi.org/10.1001/jamasurg.2019.4079.

  69. Yeung JC, Krueger T, Yasufuku K, de Perrot M, Pierre AF, Waddell TK, et al. Outcomes after transplantation of lungs preserved for more than 12 h: a retrospective study. Lancet Respir Med. 2017;5(2):119–24. https://doi.org/10.1016/S2213-2600(16)30323-X.

    Article  PubMed  Google Scholar 

  70. Levvey B, Keshavjee S, Cypel M, et al. Influence of lung donor agonal and warm ischemic times on early mortality: analyses from the ISHLT DCD Lung Transplant Registry. J Heart Lung Transplant. 2019;38(1):26–34. https://doi.org/10.1016/j.healun.2018.08.006.

    Article  PubMed  Google Scholar 

  71. Van Raemdonck DE, Keshavjee S, Levvey B, et al. 5-Year results from the ISHLT DCD Lung Transplant Registry confirm excellent recipient survival from donation after circulatory death donors [Abstract]. In: The Journal of Heart and Lung Transplantation: Elsevier Inc.; 2019. p. S103. https://doi.org/10.1016/j.healun.2019.01.241. Accessed 18 Oct 2019

  72. Villavicencio MA, Axtell AL, Spencer PJ, Heng EE, Kilmarx S, Dalpozzal N, et al. Lung transplantation from donation after circulatory death: United States and single-center experience. Ann Thorac Surg. 2018;106(6):1619–27. https://doi.org/10.1016/j.athoracsur.2018.07.024.

    Article  PubMed  Google Scholar 

  73. Warnecke G, Van Raemdonck D, Smith MA, et al. Normothermic ex-vivo preservation with the portable Organ Care System Lung device for bilateral lung transplantation (INSPIRE): a randomised, open-label, non-inferiority, phase 3 study. Lancet Respir Med. 2018;6(5):357–67. https://doi.org/10.1016/S2213-2600(18)30136-X.

    Article  PubMed  Google Scholar 

  74. Slama A, Schillab L, Barta M, et al. Standard donor lung procurement with normothermic ex vivo lung perfusion: a prospective randomized clinical trial. J Heart Lung Transplant. 2017;36(7):744–53. https://doi.org/10.1016/j.healun.2017.02.011.

    Article  PubMed  Google Scholar 

  75. Yeung JC, Zamel R, Klement W, Bai XH, Machuca TN, Waddell TK, et al. Towards donor lung recovery—gene expression changes during ex vivo lung perfusion of human lungs. Am J Transplant. 2018;18(6):1518–26. https://doi.org/10.1111/ajt.14700.

    Article  CAS  PubMed  Google Scholar 

  76. • Galasso M, Feld JJ, Watanabe Y, et al. Inactivating hepatitis C virus in donor lungs using light therapies during normothermic ex vivo lung perfusion. Nat Commun. 2019;10(1). https://doi.org/10.1038/s41467-018-08261-zNMP used as a theurapeutic platform to treat HCV-infected lungs prior to transplantation.

  77. Nakajima D, Cypel M, Bonato R, Machuca TN, Iskender I, Hashimoto K, et al. Ex vivo perfusion treatment of infection in human donor lungs. Am J Transplant. 2016;16(4):1229–37. https://doi.org/10.1111/ajt.13562.

    Article  CAS  PubMed  Google Scholar 

  78. Nakajima D, Liu M, Ohsumi A, et al. Lung lavage and surfactant replacement during ex vivo lung perfusion for treatment of gastric acid aspiration–induced donor lung injury. J Heart Lung Transplant. 2017;36(5):577–85. https://doi.org/10.1016/j.healun.2016.11.010.

    Article  PubMed  Google Scholar 

  79. Hatami S, Freed DH. Machine perfusion of donor heart: state of the art. Curr Transplant Rep. 2019;6(3):242–50. https://doi.org/10.1007/s40472-019-00251-4.

    Article  Google Scholar 

  80. Barnard CN. The operation: a human cardiac transplant: an interim report of a successful operation performed at Groote Schuur hospital, Cape Town South African. Med J. 1967;41(48):1271–4.

    CAS  Google Scholar 

  81. Van Raemdonck D, Rega F, Rex S, Neyrinck A. Machine perfusion of thoracic organs. J Thorac Dis. 2018;10(Suppl 8):S910–23. https://doi.org/10.21037/jtd.2018.02.85.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Schroder JN, D’Alessandro D, Esmailian F, et al. Successful utilization of extended criteria donor (ECD) hearts for transplantation - results of the OCS™ Heart EXPAND Trial to evaluate the effectiveness and safety of the OCS Heart system to preserve and assess ECD hearts for transplantation. J Heart Lung Transplant. 2019;38(4):S42. https://doi.org/10.1016/j.healun.2019.01.088.

    Article  Google Scholar 

  83. •• Chew HC, Iyer A, Connellan M, et al. Outcomes of donation after circulatory death heart transplantation in Australia. J Am Coll Cardiol. 2019;73(12):1447–59. https://doi.org/10.1016/j.jacc.2018.12.067First series of distantly procured DCD heart transplants, enabled by NMP.

    Article  PubMed  Google Scholar 

  84. Messer S, Page A, Axell R, et al. Outcome after heart transplantation from donation after circulatory-determined death donors. J Heart Lung Transplant. 2017;36(12):1311–8. https://doi.org/10.1016/j.healun.2017.10.021.

    Article  PubMed  Google Scholar 

  85. Hatami S, White CW, Shan S, Haromy A, Qi X, Ondrus M, et al. Myocardial functional decline during prolonged ex situ heart perfusion. Ann Thorac Surg. 2019;108(2):499–507. https://doi.org/10.1016/j.athoracsur.2019.01.076.

    Article  PubMed  Google Scholar 

  86. Lucchinetti E, Lou PH, Hatami S, Qi X, Clanachan AS, Freed DH, et al. Enhanced myocardial protection in cardiac donation after circulatory death using Intralipid ® postconditioning in a porcine model. Can J Anesth. 2019;66(6):672–85. https://doi.org/10.1007/s12630-019-01322-x.

    Article  PubMed  Google Scholar 

  87. Bishawi M, Roan JN, Milano CA, Daneshmand MA, Schroder JN, Chiang Y, et al. A normothermic ex vivo organ perfusion delivery method for cardiac transplantation gene therapy. Sci Rep. 2019;9(1):1–9. https://doi.org/10.1038/s41598-019-43737-y.

    Article  CAS  Google Scholar 

  88. Kandaswamy R, Stock PG, Gustafson SK, Skeans MA, Urban R, Fox A, et al. OPTN/SRTR 2017 annual data report: pancreas. Am J Transplant. 2019;19:124–83. https://doi.org/10.1111/ajt.15275.

    Article  PubMed  Google Scholar 

  89. Branchereau J, Renaudin K, Kervella D, et al. Hypothermic pulsatile perfusion of human pancreas: preliminary technical feasibility study based on histology. Cryobiology. 2018;85(October):56–62. https://doi.org/10.1016/j.cryobiol.2018.10.002.

    Article  CAS  PubMed  Google Scholar 

  90. Leemkuil M, Lier G, Engelse MA, Ploeg RJ, de Koning EJP, 't Hart NA, et al. Hypothermic oxygenated machine perfusion of the human donor pancreas. Transplant Direct. 2018;4(10):1–8. https://doi.org/10.1097/TXD.0000000000000829.

    Article  Google Scholar 

  91. Hamaoui K, Gowers S, Sandhu B, Vallant N, Cook T, Boutelle M, et al. Development of pancreatic machine perfusion: translational steps from porcine to human models. J Surg Res. 2018;223:263–74. https://doi.org/10.1016/j.jss.2017.11.052.

    Article  PubMed  Google Scholar 

  92. Nassar A, Liu Q, Walsh M, Quintini C. Normothermic ex vivo perfusion of discarded human pancreas. Artif Organs. 2018;42(3):334–5. https://doi.org/10.1111/aor.12985.

    Article  PubMed  Google Scholar 

  93. Kumar R, Chung WY, Runau F, et al. Ex vivo normothermic porcine pancreas: a physiological model for preservation and transplant study. Int J Surg. 2018;54(April 2018):206–15. https://doi.org/10.1016/j.ijsu.2018.04.057.

    Article  PubMed  Google Scholar 

  94. Gilbert Fernandez JJ, Febres-Cordero RG, Simpson RL. The untold story of the first hand transplant: dedicated to the memory of one of the great minds of the Ecuadorian medical community and the world. J Reconstr Microsurg. 2019;35(3):163–7. https://doi.org/10.1055/s-0038-1668535.

    Article  PubMed  Google Scholar 

  95. Dubernard J-M, Owen E, Herzberg G, Lanzetta M, Martin X, Kapila H, et al. Human hand allograft: report on first 6 months. Lancet. 1999;353:1315–20.

    Article  CAS  PubMed  Google Scholar 

  96. Devauchelle B, Badet L, Lengelé B, Morelon E, Testelin S, Michallet M, et al. First human face allograft: early report. Lancet. 2006;368(9531):203–9. https://doi.org/10.1016/S0140-6736(06)68935-6.

    Article  PubMed  Google Scholar 

  97. Cetrulo CL, Li K, Salinas HM, et al. Penis transplantation - first US experience. Ann Surg. 2018;267(5):983–8. https://doi.org/10.1097/SLA.0000000000002241.

    Article  PubMed  Google Scholar 

  98. van der Merwe A, Graewe F, Zühlke A, et al. Penile allotransplantation for penis amputation following ritual circumcision: a case report with 24 months of follow-up. Lancet. 2017;390(10099):1038–47. https://doi.org/10.1016/S0140-6736(17)31807-X.

    Article  PubMed  Google Scholar 

  99. Strome M, Stein J, Esclamado R, Hicks D, Lorenz RR, Braun W, et al. Laryngeal transplantation and 40-month follow-up. N Engl J Med. 2001;344(22):1676–9.

    Article  CAS  PubMed  Google Scholar 

  100. Levi DM, Tzakis AG, Kato T, Madariaga J, Mittal NK, Nery J, et al. Transplantation of the abdominal wall. Lancet. 2003;361:2173–6. https://doi.org/10.1016/S0140-6736(03)13769-5.

    Article  PubMed  Google Scholar 

  101. Brännström M, Johannesson L, Bokström H, Kvarnström N, Mölne J, Dahm-Kähler P, et al. Livebirth after uterus transplantation. Lancet. 2015;385:607–16. https://doi.org/10.1016/S0140-6736(14)61728-1.

    Article  PubMed  Google Scholar 

  102. Jones B, Saso S, Bracewell-Milnes T, Thum MY, Nicopoullos J, Diaz-Garcia C, et al. Human uterine transplantation: a review of outcomes from the first 45 cases. BJOG. 2019;126:1310–9. https://doi.org/10.1111/1471-0528.15863.

    Article  CAS  PubMed  Google Scholar 

  103. Thuong M, Petruzzo P, Landin L, Mahillo B, Kay S, Testelin S, et al. Vascularized composite allotransplantation – a Council of Europe position paper. Transpl Int. 2019;32:233–40. https://doi.org/10.1111/tri.13370.

    Article  PubMed  Google Scholar 

  104. McGimpsey G, Bradford TC. Limb prosthetics services and devices – critical unmet need: market analysis white paper. 2008. http://www.nist.gov/tip/wp/pswp/upload/239_limb_prosthetics_services_devices.pdf. Accessed 20 Oct 2019

  105. Organ procurement and transplantation network data as of October 31, 2019. U.S. Department of Health & Human Services. https://optn.transplant.hrsa.gov/data/. Published 2019. Accessed 20 Oct 2019

  106. Blaisdell FW. The pathophysiology of skeletal muscle ischemia and the reperfusion syndrome: a review. Vascular. 2002;10(6):620–30. https://doi.org/10.1177/096721090201000620.

    Article  Google Scholar 

  107. Burlage LC, Tessier SN, Etra JW, Uygun K, Brandacher G. Advances in machine perfusion, organ preservation, and cryobiology: potential impact on VCA. Curr Opin Organ Transplant. 2019;23(5):561–7. https://doi.org/10.1097/MOT.0000000000000567.Advances.

    Article  Google Scholar 

  108. Giwa S, Lewis JK, Alvarez L, Langer R, Roth AE, Church GM, et al. The promise of organ and tissue preservation to transform medicine. Nat Biotechnol. 2017;35(6):530–42. https://doi.org/10.1038/nbt.3889.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Burlage LC, Lellouch AG, Saviane GG, et al. First vascularized composite allotransplantations in rats after 6 hours of ex vivosubnormothermic machine perfusion using an hemoglobin oxygen carrier: a proof of concept study [abstract]. J Burn Care Res. 2019;40(Supplement_1):S133–4. https://doi.org/10.1093/jbcr/irz013.226.

    Article  Google Scholar 

  110. Salehi S, Grayson W, Brandacher G, Furtmuller G, Lopez J. Establishing a rat abdominal wall perfusion model for vca preservation [abstract]. Cryobiology. 2018;81:232. https://doi.org/10.1016/j.cryobiol.2017.12.078.

    Article  Google Scholar 

  111. Kueckelhaus M, Fischer S, Sisk G, Kiwanuka H, Bueno EM, Dermietzel A, et al. A mobile extracorporeal extremity salvage system for replantation and transplantation. Ann Plast Surg. 2016;76(3):355–60. https://doi.org/10.1097/SAP.0000000000000681.

    Article  CAS  PubMed  Google Scholar 

  112. Ozer K, Rojas-Pena A, Mendias CL, Bryner BS, Toomasian C, Bartlett RH. The effect of ex situ perfusion in a swine limb vascularized composite tissue allograft on survival up to 24 hours. J Hand Surg [Am]. 2016;41(1):3–12. https://doi.org/10.1016/j.jhsa.2015.11.003.

    Article  Google Scholar 

  113. Krezdorn N, Macleod F, Tasigiorgos S, et al. Twenty-four–hour ex vivo perfusion with acellular solution enables successful replantation of porcine forelimbs. Plast Reconstr Surg. 2019;144(4):608e–18e. https://doi.org/10.1097/prs.0000000000006084.

    Article  CAS  PubMed  Google Scholar 

  114. Werner NL, Alghanem F, Rakestraw SL, Sarver DC, Nicely B, Pietroski RE, et al. Ex situ perfusion of human limb allografts for 24 hours. Transplantation. 2017;101(3):e68–74. https://doi.org/10.1097/TP.0000000000001500.

    Article  PubMed  Google Scholar 

  115. de Vries RJ, Tessier SN, Banik PD, Nagpal S, Cronin SEJ, Ozer S, et al. Supercooling extends preservation time of human livers. Nat Biotechnol. 2019;37(10):1131–6. https://doi.org/10.1038/s41587-019-0223-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Messner F, Guo Y, Etra JW, Brandacher G. Emerging technologies in organ preservation, tissue engineering and regenerative medicine: a blessing or curse for transplantation? Transpl Int. 2019;32(7):673–85. https://doi.org/10.1111/tri.13432.

    Article  PubMed  Google Scholar 

  117. Starzl TE, Marchioro TL, Peters GN, et al. Renal heterotransplantation from baboon to man: experience with 6 cases. Transplantation. 1964;2(6):752–76. https://doi.org/10.1097/00007890-196411000-00009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Längin M, Mayr T, Reichart B, Michel S, Buchholz S, Guethoff S, et al. Consistent success in life-supporting porcine cardiac xenotransplantation. Nature. 2018;564(7736):430–3. https://doi.org/10.1038/s41586-018-0765-z.

    Article  CAS  PubMed  Google Scholar 

  119. Ramackers W, Werwitzke S, Klose J, Friedrich L, Johanning K, Bergmann S, et al. Investigation of the influence of xenoreactive antibodies on activation of complement and coagulation in an ex vivo perfusion animal study using porcine kidneys. Transpl Int. 2019;32(5):546–56. https://doi.org/10.1111/tri.13396.

    Article  CAS  PubMed  Google Scholar 

  120. Abicht JM, Sfriso R, Reichart B, et al. Multiple genetically modified GTKO/hCD46/HLA-E/hβ2−mg porcine hearts are protected from complement activation and natural killer cell infiltration during ex vivo perfusion with human blood. Xenotransplantation. 2018;25(5):1–11. https://doi.org/10.1111/xen.12390.

    Article  Google Scholar 

  121. Burdorf L, Azimzadeh AM, Pierson RNI. Progress and challenges in lung xenotransplantation - an update. Curr Opin Organ Transplant. 2018;23(6):621–7. https://doi.org/10.1097/MOT.0000000000000582.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Center for Engineering in Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA

    Cray V. Noah, Siavash Raigani & Korkut Uygun

  2. Division of Transplant Surgery, Massachusetts General Hospital, Boston, MA, USA

    Cray V. Noah, Siavash Raigani & Heidi Yeh

  3. Vascularized Composite Allotransplantation Laboratory, Division of Plastic Surgery, Harvard Medical School and Massachusetts General Hospital Shriners Hospital for Children, Boston, MA, USA

    Philipp Tratnig-Frankl & Curtis L. Cetrulo Jr

  4. Shriners Hospital for Children, Boston, MA, USA

    Philipp Tratnig-Frankl, Siavash Raigani, Curtis L. Cetrulo Jr & Korkut Uygun

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Noah, C.V., Tratnig-Frankl, P., Raigani, S. et al. Moving the Margins: Updates on the Renaissance in Machine Perfusion for Organ Transplantation. Curr Transpl Rep 7, 114–123 (2020). https://doi.org/10.1007/s40472-020-00277-z

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