Normothermic ex-vivo liver perfusion: where do we stand and where to reach?

References

• OPTN National Data. Organ Procurement Transplantation Network. United States; 2016.
   Google Scholar
• Jassem W, Fuggle S, Thompson R, et al. Effect of ischemic preconditioning on the genomic response to reperfusion injury in deceased donor liver transplantation. Liver Transpl. 2009;15(12):1750–1765.
   PubMed Web of Science ®Google Scholar
• Amador A, Grande L, Martí J, et al. Ischemic pre-conditioning in deceased donor liver transplantation: a prospective randomized clinical trial. Am J Transplant. 2007;7(9):2180–2189.
   PubMed Web of Science ®Google Scholar
• Belzer FO, Southard JH. Principles of solid-organ preservation by cold storage. Transplantation. 1988;45(4):673–676.
   PubMed Web of Science ®Google Scholar
• Rauen U, Groot H D. New insights into the cellular and molecular mechanisms of cold storage injury. J Investig Med. 2004;52(5):299–309.
   PubMed Web of Science ®Google Scholar
• Feng XN, Xu X, Zheng S S. Current status and perspective of liver preservation solutions. Hepatobiliary Pancreat Dis Int. 2006;5(4):490–494.
   PubMedGoogle Scholar
• Guibert EE, Petrenko AY, Balaban CL, et al. Organ preservation: current concepts and new strategies for the next decade. Transfus Med Hemotherapy. 2011;38(2):125–142.
   PubMed Web of Science ®Google Scholar
• Baskin-Bey ES, Washburn K, Feng S, et al. Clinical trial of the pan-caspase inhibitor, IDN-6556, in human liver preservation injury. Am J Transplant. 2007;7(1):218–225.
   PubMed Web of Science ®Google Scholar
• Busuttil RW, Lipshutz GS, Kupiec-Weglinski JW, et al. RPSGL-Ig for improvement of early liver allograft function: A double-blind, placebo-controlled, single-center phase II study. Am J Transplant. 2011;11(4):786–797.
   PubMed Web of Science ®Google Scholar
• Jamieson RW, Zilvetti M, Roy D, et al. Hepatic steatosis and normothermic perfusion—preliminary experiments in a porcine model. Transplantation. 2011;92(3):289–295.
   PubMed Web of Science ®Google Scholar
• Jayant K, Reccia I, Virdis FSAM. The role of normothermic perfusion in liver transplantation (TRaNsIT Study): a systematic review of preliminary studies. HPB Surg. 2018;2018:20186360423.
   Google Scholar
• Hosgood SA. Renal transplantation after ex vivo normothermic perfusion: the first clinical study. Am J Transplant. 2013;13(5):1246–1252.
   PubMed Web of Science ®Google Scholar
• Brockmann J, Reddy S, Coussios C, et al. Normothermic perfusion: a new paradigm for organ preservation. Ann Surg. 2009;250(1):1–6.
   PubMed Web of Science ®Google Scholar
• Ali F, Dua A, Cronin DC. Changing paradigms in organ preservation and resuscitation. Curr Opin Organ Transplant. 2015;20(2):152–158.
   PubMed Web of Science ®Google Scholar
• Sutton ME, Op Den Dries S, Karimian N, et al. Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion. PLoS One. 2014;9(11):e110642.
   PubMed Web of Science ®Google Scholar
• Op Den Dries S, Karimian N, Sutton ME, et al. Ex vivo normothermic machine perfusion and viability testing of discarded human donor livers. Am J Transpl. 2013;13(5):1327–1335.
   PubMed Web of Science ®Google Scholar
• Yska MJ, Buis CI, Monbaliu D, et al. The role of bile salt toxicity in the pathogenesis of bile duct injury after non-heart-beating porcine liver transplantation. Transplantation. 2008;85(11):1625–1631.
   PubMed Web of Science ®Google Scholar
• Graham JA, Guarrera JV. ”Resuscitation” of marginal liver allografts for transplantation with machine perfusion technology. J Hepatol. 2014;61(2):418–431.
   PubMed Web of Science ®Google Scholar
• Mergental H, Roll GR. Normothermic machine perfusion of the liver. Clin Liver Dis. 2017;10:97–99.
   Google Scholar
• Vogel T, Brockmann JG, Friend PJ. Ex-vivo normothermic liver perfusion: an update. Curr Opin Organ Transplant. 2010;15(2):167–172.
   PubMed Web of Science ®Google Scholar
• Ravikumar R, Jassem W, Mergental H, et al. Liver transplantation after ex vivo normothermic machine preservation: a phase 1 (first-in-man) clinical trial. Am J Transpl. 2016;16(6):1779–1787.
   PubMed Web of Science ®Google Scholar
• Jochmans I, Akhtar MZ, Nasralla D, et al. Past, present, and future of dynamic kidney and liver preservation and resuscitation. Am J Transplant. 2016;16(9):2545–2555.
   Google Scholar
• Minor T, Efferz P, Fox M, et al. Controlled oxygenated rewarming of cold stored liver grafts by thermally graduated machine perfusion prior to reperfusion. Am J Transplant. 2013;13(6):1450–1460.
   PubMed Web of Science ®Google Scholar
• Ceresa CDL, Nasralla D, Coussios CC, et al. The case for normothermic machine perfusion in liver transplantation. Liver Transplant Off Publ Am Assoc Study Liver Dis Int Liver Transplant Soc. 2018;24(2):269–275.
   Google Scholar
• Bral M, Gala-Lopez B, Bigam D, et al. Preliminary single-center Canadian experience of human normothermic ex vivo liver perfusion. Results Clinical Trial Am J Transplant. 2017;17(4):1071–1080.
   Google Scholar
• Selzner M, Goldaracena N, Echeverri J, et al. Normothermic ex vivo liver perfusion using steen solution as perfusate for human liver transplantation: first North American results. Liver Transpl. 2016;22(11):1501–1508.
   PubMed Web of Science ®Google Scholar
• Liu Q, Soliman B, Iuppa G, et al. First report of human liver transplantation after normothermic machine perfusion (NMP) in the United States. Am J Transpl. 2017;17(Suppl3).
   Google Scholar
• Nasralla D, Coussios CC, Mergental H, et al. A randomized trial of normothermic preservation in liver transplantation. Nature. 2018;557(7703):50–56.
   PubMed Web of Science ®Google Scholar
• Nassar A, Liu Q, Farias K, et al. Ex vivo normothermic machine perfusion is safe, simple, and reliable: results from a large animal model. Surg Innov. 2015;22(1):61–69.
   PubMed Web of Science ®Google Scholar
• Watson CJE, Kosmoliaptsis V, Randle LV, et al. Normothermic perfusion in the assessment and preservation of declined livers before transplantation: hyperoxia and vasoplegia-important lessons from the first 12 cases. Transplantation. 2017;101(5):1084–1098.
   PubMed Web of Science ®Google Scholar
• Liu Q, Nassar A, Farias K, et al. Comparing normothermic machine perfusion preservation with different perfusates on porcine livers from donors after circulatory death. Am J Transplant. 2016;16(3):794–807.
   PubMed Web of Science ®Google Scholar
• Izamis ML, Tolboom H, Uygun B, et al. Resuscitation of ischemic donor livers with normothermic machine perfusion: a metabolic flux analysis of treatment in rats. PLoS One. 2013;8(7):e69758.
   PubMed Web of Science ®Google Scholar
• Schlegel A, Kron P, Graf R, et al. Warm vs cold perfusion techniques to rescue rodent liver grafts. J Hepatol. 2014;61(6):1267–1275.
   PubMed Web of Science ®Google Scholar
• Nui A, Katsuramaki T, Kikuchi H, et al. Successful ex vivo normothermic liver perfusion with purely artificial products using artificial blood. Int J Artif Organs. 2003;26(1):46–52.
   PubMed Web of Science ®Google Scholar
• Fontes P, Lopez R, Van Der Plaats A, et al. Liver preservation with machine perfusion and a newly developed cell-free oxygen carrier solution under subnormothermic conditions. Am J Transpl. 2015;15(2):381–394.
   PubMed Web of Science ®Google Scholar
• Laing RW, Mergental H, Yap C, 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:e017733.
   PubMed Web of Science ®Google Scholar
• Kim HW, Greenburg AG. Artificial oxygen carriers as red blood cell substitutes: a selected review and current status. Artif Organs. 2004;28(9):813–828.
   PubMed Web of Science ®Google Scholar
• St. Peter SD, Imber CJ, Friend PJ. Liver and kidney preservation by perfusion. Lancet. 2002;359(9306):604–613.
   PubMed Web of Science ®Google Scholar
• Imber CJ, St Peter SD, Lopez De Cenarruzabeitia I, et al. Advantages of normothermic perfusion over cold storage in liver preservation. Transplantation. 2002;73(5):701–709.
   PubMed Web of Science ®Google Scholar
• Lee CY, Mangino MJ. Preservation methods for kidney and liver. Organogenesis. 2009;5(3):105–112.
   PubMed Web of Science ®Google Scholar
• Matton APM, Burlage LC, Van Rijn R, et al. Normothermic machine perfusion of donor livers without the need for human blood products. Liver Transpl. 2018;24(4):528–538.
   PubMed Web of Science ®Google Scholar
• Marecki H, Bozorgzadeh A, Porte R, et al. Liver ex-vivo machine perfusion preservation: a review of the methodology and results of large animal studies and clinical trials. Liver Transpl. 2017;23(5):679–695.
   PubMed Web of Science ®Google Scholar
• Eshmuminov D, Leoni F, Schneider MA, et al. Perfusion settings and additives in liver normothermic machine perfusion with red blood cells as oxygen carrier. A systematic review of human and porcine perfusion protocols. Transpl Int. 2018. doi: 10.1111/tri.13306. [ Epub ahead of print].
   Web of Science ®Google Scholar
• Mergental H, Perera MTPR, Laing RW, et al. Transplantation of declined liver allografts following normothermic ex-situ evaluation. Am J Transpl. 2016;16(11):3235–3245.
   PubMed Web of Science ®Google Scholar
• Reiling J, Lockwood DSR, Simpson AH, et al. Urea production during normothermic machine perfusion: price of success?. Liver Transpl. 2015;21(5):700–703.
   PubMed Web of Science ®Google Scholar
• He X, Guo Z, Zhao Q, et al. The first case of ischemia-free organ transplantation in humans: a proof of concept. Am J Transpl. 2018;18(3):737–744.
   PubMed Web of Science ®Google Scholar
• Liu Q, Nassar A, Buccini L, et al. Lipid metabolism and functional assessment of discarded human livers with steatosis undergoing 24 hours normothermic machine perfusion. Liver Transpl. 2017;24(2):233–245.
   Web of Science ®Google Scholar
• Goldaracena N, Echeverri J, Spetzler VN, et al. Anti-inflammatory signaling during ex vivo liver perfusion improves the preservation of pig liver grafts before transplantation. Liver Transpl. 2016;22(11):1573–1583.
   PubMed Web of Science ®Google Scholar
• Nassar A, Liu Q, Farias K, et al. Role of vasodilation during normothermic machine perfusion of DCD porcine livers. Int J Artif Organs. 2014;37(2):165–172.
   PubMed Web of Science ®Google Scholar
• Spoelstra-De Man AM, Smit B, Oudemans-Van Straaten HM, et al. Cardiovascular effects of hyperoxia during and after cardiac surgery. Anaesthesia. 2015;70(11):1307–1319.
   PubMed Web of Science ®Google Scholar
• Weigand K, Brost S, Steinebrunner N, et al. Ischemia/reperfusion injury in liver surgery and transplantation: pathophysiology. HPB Surg. 2012;2012:176723.
   PubMedGoogle Scholar
• Zinchuk VV, Khodosovsky MN, Maslakov DA. Influence of different oxygen modes on the blood oxygen transport and prooxidant-antioxidant status during hepatic ischemia/reperfusion. Physiol Res. 2003;52(5):533–544.
   PubMed Web of Science ®Google Scholar
• Bral M, Gala-Lopez B, Thiesen A, et al. Determination of minimal hemoglobin level necessary for normothermic porcine ex situ liver perfusion. Transplantation. 2018. [ Epub ahead of print].
   PubMed Web of Science ®Google Scholar
• Jay CL, Skaro AI, Ladner DP, et al. Comparative effectiveness of donation after cardiac death versus donation after brain death liver transplantation: recognizing who can benefit. Liver Transpl. 2012;18(6):630–640.
   PubMed Web of Science ®Google Scholar
• Fondevila C, Hessheimer AJ, Flores E, et al. Applicability and results of Maastricht type 2 donation after cardiac death liver transplantation. Am J Transplant. 2012;12(1):162–170.
   PubMed Web of Science ®Google Scholar
• Xia W, Ke Q, Wang Y, et al. Donation after cardiac death liver transplantation: graft quality evaluation based on pretransplant liver biopsy. Liver Transpl. 2015;21(6):838–846.
   PubMed Web of Science ®Google Scholar
• Vairetti M, Ferrigno A, Rizzo V, et al. Subnormothermic machine perfusion protects against rat liver preservation injury: a comparative evaluation with conventional cold storage. Transplant Proc. 2007;39(6):1765–1767.
   PubMed Web of Science ®Google Scholar
• Ferrigno A, Rizzo V, Boncompagni E, et al. Machine perfusion at 20°C reduces preservation damage to livers from non-heart beating donors. Cryobiology. 2011;62(2):152–158.
   PubMed Web of Science ®Google Scholar
• Bessems M, Doorschodt BM, Kolkert JLP, et al. Preservation of steatotic livers: a comparison between cold storage and machine perfusion preservation. Liver Transpl. 2007;13(4):497–504.
   PubMed Web of Science ®Google Scholar
• Black SM, Whitson BA, Velayutham M. EPR spectroscopy as a predictive tool for the assessment of marginal donor livers perfused on a normothermic ex vivo perfusion circuit. Med Hypotheses. 2014;82(5):627–630.
   PubMed Web of Science ®Google Scholar
• Karangwa SA, Burlage LC, Adelmeijer J, et al. Activation of fibrinolysis, but not coagulation, during end-ischemic ex situ normothermic machine perfusion of human donor livers. Transplantation. 2017;101(2):e42–e48.
   PubMed Web of Science ®Google Scholar
• Watson CJE, Kosmoliaptsis V, Pley C, et al. Observations on the ex situ perfusion of livers for transplantation. Am J Transpl. 2018. doi: 10.1111/ajt.14687. [ Epub ahead of print].
   Web of Science ®Google Scholar
• Ayanoglu HO, Ulukaya S, Tokat Y. Causes of postreperfusion syndrome in living or cadaveric donor liver transplantations. Transplant Proc. 2003;35(4):1442–1444.
   PubMed Web of Science ®Google Scholar
• Fukazawa K, Yamada Y, Gologorsky E, et al. Hemodynamic recovery following postreperfusion syndrome in liver transplantation. J Cardiothorac Vasc Anesth. 2014;28(4):994–1002.
   PubMed Web of Science ®Google Scholar
• Bukowicka B, Akar RA, Olszewska A, et al. The occurrence of postreperfusion syndrome in orthotopic liver transplantation and its significance in terms of complications and short-term survival. Ann Transplant. 2011;16(2):26–30.
   PubMed Web of Science ®Google Scholar
• Chung IS, Kim HY, Shin YH, et al. Incidence and predictors of post-reperfusion syndrome in living donor liver transplantation. Clin Transplant. 2012;26(4):539–543.
   PubMed Web of Science ®Google Scholar
• Chui AKK, Shi L, Tanaka K, et al. Postreperfusion syndrome in orthotopic liver transplantation. Transplant Proc. 2000;32(7):2116–2117.
   PubMed Web of Science ®Google Scholar
• Siniscalchi A, Dante A, Spedicato S, et al. Hyperdynamic circulation in acute liver failure: reperfusion syndrome and outcome following liver transplantation. Transplant Proc. 2010;42(4):1197–1199.
   PubMed Web of Science ®Google Scholar
• Martell M, Coll M, Ezkurdia N, et al. Physiopathology of splanchnic vasodilation in portal hypertension. World J Hepatol. 2010;2(6):208–220.
   PubMedGoogle Scholar
• Gracia-Sancho J, Maeso-Diaz R, Fernandez-Iglesias A, et al. New cellular and molecular targets for the treatment of portal hypertension. Hepatol Int. 2015;9(2):183–191.
   PubMed Web of Science ®Google Scholar
• Mahboub P, Bozorgzadeh A, Martins PN. Potential approaches to improve the outcomes of donation after cardiac death liver grafts. World J Transplant. 2016;6(2):314–320.
   PubMedGoogle Scholar
• Angelico R, Perera MTPR, Ravikumar R, et al. Normothermic machine perfusion of deceased donor liver grafts is associated with improved postreperfusion hemodynamics. Transplant Direct. 2016;2(9):e97.
   PubMed Web of Science ®Google Scholar
• Russo L, Gracia-Sancho J, García-Calderó H, et al. Addition of simvastatin to cold storage solution prevents endothelial dysfunction in explanted rat livers. Hepatology. 2012;55(3):921–930.
   PubMed Web of Science ®Google Scholar
• Boehnert MU, Yeung JC, Bazerbachi F, et al. Normothermic acellular EX vivo liver perfusion reduces liver and bile duct injury of pig livers retrieved after cardiac death. Am J Transplant. 2013;13(6):1441–1449.
   PubMed Web of Science ®Google Scholar
• Le Dinh H, De Roover A, Kaba A, et al. Donation after cardio-circulatory death liver transplantation. World J Gastroenterol. 2012;18(33):4491–4506.
   PubMed Web of Science ®Google Scholar
• Pareja E, Cortes M, Navarro R, et al. Vascular complications after orthotopic liver transplantation. Transplant Proc. 2010;42(8):2970–2972.
   PubMed Web of Science ®Google Scholar
• Selton J, Schlegal A, De Jonge J, et al. Hypo- and normothermic perfusion of the liver: which way to go?. Best Pract Res Clin Gastroenterol. 2017;31(2):171–179.
   PubMed Web of Science ®Google Scholar
• Tang JX, Na N, Li JJ, et al. Outcomes of controlled donation after cardiac death compared with donation after brain death in liver transplantation: a systematic review and meta-analysis. Transplant Proc. 2018;50(1):33–41.
   PubMed Web of Science ®Google Scholar
• Olthoff KM, Kulik L, Samstein B, et al. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl. 2010;16(8):943–949.
   PubMed Web of Science ®Google Scholar
• Croome KP, Wall W, Quan D, et al. Evaluation of the updated definition of early allograft dysfunction in donation after brain death and donation after cardiac death liver allografts. Hepatobiliary Pancreat Dis Int. 2012;11(4):372–376.
   PubMed Web of Science ®Google Scholar
• Nasralla D, Ploeg R, Coussios CFP,, . Outcomes from a multinational randomised controlled trial comparing normothermic machine perfusion with static cold storage in human liver transplantation. Am J Transpl. 2017;(Suppl 3).
   Google Scholar
• Jay CL, Lyuksemburg V, Ladner DP, et al. Ischemic cholangiopathy after controlled donation after cardiac death liver transplantation. Ann Surg. 2011;253(2):259–264.
   PubMed Web of Science ®Google Scholar
• Op Den Dries S, Me S, Lisman T, et al. Protection of bile ducts in liver transplantation: looking beyond ischemia. Transplantation. 2011;92(4):373–379.
   PubMed Web of Science ®Google Scholar
• Op Den Dries S, Westerkamp AC, Karimian N, et al. Injury to peribiliary glands and vascular plexus before liver transplantation predicts formation of non-anastomotic biliary strictures. J Hepatol. 2014;60(6):1172–1179.
   PubMed Web of Science ®Google Scholar
• Op Den Dries S, Karimian N, Westerkamp AC, et al. Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers. Liver Transpl. 2016;22(7):994–1005.
   PubMed Web of Science ®Google Scholar
• Liu Q, Nassar A, Farias K, et al. Sanguineous normothermic machine perfusion improves hemodynamics and biliary epithelial regeneration in donation after cardiac death porcine livers. Liver Transpl. 2014;20(8):987–999.
   PubMed Web of Science ®Google Scholar
• Shapiro AMJ. Normothermic machine perfusion: a new world deserving careful exploration. Am J Transplant. 2017;17(7): 1958. Response to.
   PubMed Web of Science ®Google Scholar
• Parsons RF, Guarrera JV. Preservation solutions for static cold storage of abdominal allografts. Curr Opin Organ Transplant. 2014;19(2):100–107.
   PubMed Web of Science ®Google Scholar
• Vogel T, Brockmann JG, Pigott D, et al. Successful transplantation of porcine liver grafts following 48-hour normothermic preservation. PLoS One. 2017;12(11):e0188494.
   PubMed Web of Science ®Google Scholar
• Nebrig M, Neuhaus P, Pascher A. Advances in the management of the explanted donor liver. Nat Rev Gastroenterol Hepatol. 2014;11(8):489–496.
   PubMed Web of Science ®Google Scholar
• Organ Donation and Transplantation Activity Report. NHS Blood Transpl. 2016/17. p. 2017.
   Google Scholar
• Andrews PA, Burnapp L, Manas D. Summary of the british transplantation society guidelines for transplantation from donors after deceased circulatory death. Transplantation. 2014;97(3):265–270.
   PubMed Web of Science ®Google Scholar
• Fondevila C, Hessheimer AJ, Maathuis M-HJ, et al. Superior preservation of DCD livers with continuous normothermic perfusion. Ann Surg. 2011;254(6):1000–1007.
   PubMed Web of Science ®Google Scholar
• Reccia I, Kumar J, Akladios C, et al. Non-alcoholic fatty liver disease: a sign of systemic disease. Metabolism. 2017;72:94–108.
   PubMed Web of Science ®Google Scholar
• Al S, Ob L, Aas D, et al. The biopsied donor liver: incorporating macrosteatosis into high-risk donor assessment. Liver Transpl. 2010;16(7):874–884.
   PubMed Web of Science ®Google Scholar
• Angele MK, Rentsch M, Hartl WH, et al. Effect of graft steatosis on liver function and organ survival after liver transplantation. Am J Surg. 2008;195(2):214–220.
   PubMed Web of Science ®Google Scholar
• Perez-Daga JA, Santoyo J, Suarez MA, et al. Influence of degree of hepatic steatosis on graft function and postoperative complications of liver transplantation. Transpl Proc. 2006;38(8):2468–2470.
   PubMed Web of Science ®Google Scholar
• Li J, Liu B, Yan LN, et al. Reversal of graft steatosis after liver transplantation: prospective study. Transplant Proc. 2009;41(9):3560–3563.
   PubMed Web of Science ®Google Scholar
• Westerkamp AC, De Boer MT, Van Den Berg AP, et al. Similar outcome after transplantation of moderate macrovesicular steatotic and nonsteatotic livers when the cold ischemia time is kept very short. Transpl Int. 2015;28(3):319–329.
   PubMed Web of Science ®Google Scholar
• Okamura Y, Hata K, Tanaka H, et al. Impact of subnormothermic machine perfusion preservation in severely steatotic rat livers: a detailed assessment in an isolated setting. Am J Transplant. 2017;17(5):1204–1215.
   PubMed Web of Science ®Google Scholar
• Nagrath D, Xu H, Tanimura Y, et al. Metabolic preconditioning of donor organs: defatting fatty livers by normothermic perfusion ex vivo. Metab Eng. 2009;11(4–5):274–283.
   PubMed Web of Science ®Google Scholar
• Banan B, Watson R, Xu M, et al. Development of a normothermic extracorporeal liver perfusion system toward improving viability and function of human extended criteria donor livers. Liver Transpl. 2016;22(7):979–993.
   PubMed Web of Science ®Google Scholar
• Hu J, Wang Z, Tan C-J, et al. Plasma microRNA, a potential biomarker for acute rejection after liver transplantation. Transplantation. 2013;95(8):991–999.
   PubMed Web of Science ®Google Scholar
• Germani G, Rodriguez-Castro K, Russo FP, et al. Markers of acute rejection and graft acceptance in liver transplantation. World J Gastroenterol. 2015;21(4):1061–1068.
   PubMed Web of Science ®Google Scholar
• Schmuck RB, Reutzel-Selke A, Raschzok N, et al. Bile: miRNA pattern and protein-based biomarkers may predict acute cellular rejection after liver transplantation. Biomarkers. 2017;22(1):19–27.
   PubMed Web of Science ®Google Scholar
• Farid WR, Pan Q, Van Der Meer AJP, et al. Hepatocyte-derived microRNAs as serum biomarkers of hepatic injury and rejection after liver transplantation. Liver Transpl. 2012;18(3):290–297.
   PubMed Web of Science ®Google Scholar
• Andaloussi S EL, Mager I, Breakefield XO, et al. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013;12(5):347–357.
   PubMed Web of Science ®Google Scholar
• Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015;33(9):941–951.
   PubMed Web of Science ®Google Scholar
• Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013;200(4):373–383.
   PubMed Web of Science ®Google Scholar
• Camussi G, Quesenberry PJ. Perspective of the potential therapeutic uses of vesicles. Exosomes Microvesicles. 2013;1:6.
   Google Scholar
• Herrera MB, Fonsato V, Bruno S, et al. Human liver stem cells improve liver injury in a model of fulminant liver failure. Hepatology. 2013;57(1):311–319.
   PubMed Web of Science ®Google Scholar
• Navarro-Tableros V, Herrera Sanchez MB, FIGliolini F, et al. Recellularization of rat liver scaffolds by human liver stem cells. Tissue Eng. 2015;21(11–12):1929–1939.
   Google Scholar
• Nojima H, Freeman CM, Schuster RM, et al. Hepatocyte exosomes mediate liver repair and regeneration via sphingosine-1-phosphate. J Hepatol. 2016;64(1):60–68.
   PubMed Web of Science ®Google Scholar
• Masyuk AI, Huang BQ, Ward CJ, et al. Biliary exosomes influence cholangiocyte regulatory mechanisms and proliferation through interaction with primary cilia. Am J Physiol Gastrointest Liver Physiol. 2010;299(4):G990–999.
   PubMed Web of Science ®Google Scholar
• Herrera MB, Bruno S, Buttiglieri S, et al. Isolation and characterization of a stem cell population from adult human liver. Stem Cells. 2006;24(12):2840–2850.
   PubMed Web of Science ®Google Scholar
• Herrera MB, Fonsato V, Gatti S, et al. Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats. J Cell Mol Med. 2010;14(6B):1605–1618.
   PubMed Web of Science ®Google Scholar
• Gravante G, Ong SL, Metcalfe MS, et al. Effects of hypoxia due to isovolemic hemodilution on an ex vivo normothermic perfused liver model. J Surg Res. 2010;160(1):73–80.
   PubMed Web of Science ®Google Scholar
• Fonsato V, Collino F, Herrera MB, et al. Human liver stem cell-derived microvesicles inhibit hepatoma growth in SCID mice by delivering antitumor microRNAs. Stem Cells. 2012;30(9):1985–1998.
   PubMed Web of Science ®Google Scholar
• Akyurekli C, Le Y, Richardson RB, et al. A systematic review of preclinical studies on the therapeutic potential of mesenchymal stromal cell-derived microvesicles. Stem Cell Rev Reports. 2015;11(1):150–160.
   PubMed Web of Science ®Google Scholar
• Biancone L, Bruno S, Deregibus MC, et al. Therapeutic potential of mesenchymal stem cell-derived microvesicles. Nephrol Dial Transplant. 2012;27(8):3037–3042.
   PubMed Web of Science ®Google Scholar
• Rigo F, De Stefano N, Navarro-Tableros V, et al. Extracellular vesicles from human liver stem cells reduce injury in an ex vivo normothermic hypoxic rat liver perfusion model. Transplantation. 2018;102(5):e205–210.
   PubMed Web of Science ®Google Scholar