Current Status and Future Perspectives on Machine Perfusion: A Treatment Platform to Restore and Regenerate Injured Lungs Using Cell and Cytokine Adsorption Therapy

Anna Niroomand, Gabriel Hirdman, Franziska Olm, Sandra Lindstedt, Anna Niroomand, Gabriel Hirdman, Franziska Olm, Sandra Lindstedt

Abstract

Since its advent in the 1990's, ex vivo lung perfusion (EVLP) has been studied and implemented as a tool to evaluate the quality of a donor organ prior to transplantation. It provides an invaluable window of opportunity for therapeutic intervention to render marginal lungs viable for transplantation. This ultimately aligns with the need of the lung transplant field to increase the number of available donor organs given critical shortages. As transplantation is the only option for patients with end-stage lung disease, advancements in technology are needed to decrease wait-list time and mortality. This review summarizes the results from the application of EVLP as a therapeutic intervention and focuses on the use of the platform with regard to cell therapies, cell product therapies, and cytokine filtration among other technologies. This review will summarize both the clinical and translational science being conducted in these aspects and will highlight the opportunities for EVLP to be developed as a powerful tool to increase the donor lung supply.

Keywords: EVLP; cell therapy; cytokine adsorption; extracellular vesicles; lung transplantation; machine perfusion; mesenchymal stromal cells.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Emerging interventions during ex vivo lung perfusion (EVLP).

References

    1. De Perrot M., Liu M., Waddell T.K., Keshavjee S. Ischemia-reperfusion-induced lung injury. Am. J. Respir. Crit. Care Med. 2003;167:490–511. doi: 10.1164/rccm.200207-670SO.
    1. Ghaidan H., Fakhro M., Andreasson J., Pierre L., Ingemansson R., Lindstedt S. Ten year follow-up of lung transplantations using initially rejected donor lungs after reconditioning using ex vivo lung perfusion. J. Cardiothorac. Surg. 2019;14:125. doi: 10.1186/s13019-019-0948-1.
    1. Ingemansson R., Eyjolfsson A., Mared L., Pierre L., Algotsson L., Ekmehag B., Gustafsson R., Johnsson P., Koul B., Lindstedt S., et al. Clinical transplantation of initially rejected donor lungs after reconditioning ex vivo. Ann. Thorac. Surg. 2009;87:255–260. doi: 10.1016/j.athoracsur.2008.09.049.
    1. Lindstedt S., Hlebowicz J., Koul B., Wierup P., Sjogren J., Gustafsson R., Steen S., Ingemansson R. Comparative outcome of double lung transplantation using conventional donor lungs and non-acceptable donor lungs reconditioned ex vivo. Interact. Cardiovasc. Thorac. Surg. 2011;12:162–165. doi: 10.1510/icvts.2010.244830.
    1. Steen S., Ingemansson R., Eriksson L., Pierre L., Algotsson L., Wierup P., Liao Q., Eyjolfsson A., Gustafsson R., Sjoberg T. First human transplantation of a nonacceptable donor lung after reconditioning ex vivo. Ann. Thorac. Surg. 2007;83:2191–2194. doi: 10.1016/j.athoracsur.2007.01.033.
    1. Machuca T.N., Cypel M. Ex vivo lung perfusion. J. Thorac. Dis. 2014;6:1054–1062. doi: 10.3978/j.issn.2072-1439.2014.07.12.
    1. Yeung J.C., Krueger T., Yasufuku K., de Perrot M., Pierre A.F., Waddell T.K., Singer L.G., Keshavjee S., Cypel M. Outcomes after transplantation of lungs preserved for more than 12 h: A retrospective study. Lancet Respir. Med. 2017;5:119–124. doi: 10.1016/S2213-2600(16)30323-X.
    1. De Wolf J., Glorion M., Jouneau L., Estephan J., Leplat J.J., Blanc F., Richard C., Urien C., Roux A., Le Guen M., et al. Challenging the Ex Vivo Lung Perfusion Procedure With Continuous Dialysis in a Pig Model. Transplantation. 2021 doi: 10.1097/TP.0000000000003931. in press .
    1. Wang X., Parapanov R., Debonneville A., Wang Y., Abdelnour-Berchtold E., Gonzalez M., Gronchi F., Perentes J.Y., Ris H.B., Eckert P., et al. Treatment with 3-aminobenzamide during ex vivo lung perfusion of damaged rat lungs reduces graft injury and dysfunction after transplantation. Am. J. Transpl. 2020;20:967–976. doi: 10.1111/ajt.15695.
    1. Lonati C., Battistin M., Dondossola D.E., Bassani G.A., Brambilla D., Merighi R., Leonardi P., Carlin A., Meroni M., Zanella A., et al. NDP-MSH treatment recovers marginal lungs during ex vivo lung perfusion (EVLP) Peptides. 2021;141:170552. doi: 10.1016/j.peptides.2021.170552.
    1. Van Raemdonck D., Neyrinck A., Rega F., Devos T., Pirenne J. Machine perfusion in organ transplantation: A tool for ex-vivo graft conditioning with mesenchymal stem cells? Curr. Opin. Organ. Transpl. 2013;18:24–33. doi: 10.1097/MOT.0b013e32835c494f.
    1. Lange C., Togel F., Ittrich H., Clayton F., Nolte-Ernsting C., Zander A.R., Westenfelder C. Administered mesenchymal stem cells enhance recovery from ischemia/reperfusion-induced acute renal failure in rats. Kidney Int. 2005;68:1613–1617. doi: 10.1111/j.1523-1755.2005.00573.x.
    1. Togel F.E., Westenfelder C. Mesenchymal stem cells: A new therapeutic tool for AKI. Nat. Rev. Nephrol. 2010;6:179–183. doi: 10.1038/nrneph.2009.229.
    1. Tan J., Wu W., Xu X., Liao L., Zheng F., Messinger S., Sun X., Chen J., Yang S., Cai J., et al. Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: A randomized controlled trial. JAMA. 2012;307:1169–1177. doi: 10.1001/jama.2012.316.
    1. Pan G.Z., Yang Y., Zhang J., Liu W., Wang G.Y., Zhang Y.C., Yang Q., Zhai F.X., Tai Y., Liu J.R., et al. Bone marrow mesenchymal stem cells ameliorate hepatic ischemia/reperfusion injuries via inactivation of the MEK/ERK signaling pathway in rats. J. Surg. Res. 2012;178:935–948. doi: 10.1016/j.jss.2012.04.070.
    1. Popp F.C., Renner P., Eggenhofer E., Slowik P., Geissler E.K., Piso P., Schlitt H.J., Dahlke M.H. Mesenchymal stem cells as immunomodulators after liver transplantation. Liver. Transpl. 2009;15:1192–1198. doi: 10.1002/lt.21862.
    1. Gregorini M., Corradetti V., Pattonieri E.F., Rocca C., Milanesi S., Peloso A., Canevari S., De Cecco L., Dugo M., Avanzini M.A., et al. Perfusion of isolated rat kidney with Mesenchymal Stromal Cells/Extracellular Vesicles prevents ischaemic injury. J. Cell Mol. Med. 2017;21:3381–3393. doi: 10.1111/jcmm.13249.
    1. De Perrot M., Sekine Y., Fischer S., Waddell T.K., McRae K., Liu M., Wigle D.A., Keshavjee S. Interleukin-8 release during early reperfusion predicts graft function in human lung transplantation. Am. J. Respir. Crit. Care Med. 2002;165:211–215. doi: 10.1164/ajrccm.165.2.2011151.
    1. Islam M.N., Das S.R., Emin M.T., Wei M., Sun L., Westphalen K., Rowlands D.J., Quadri S.K., Bhattacharya S., Bhattacharya J. Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nat. Med. 2012;18:759–765. doi: 10.1038/nm.2736.
    1. Lee J.W., Krasnodembskaya A., McKenna D.H., Song Y., Abbott J., Matthay M.A. Therapeutic effects of human mesenchymal stem cells in ex vivo human lungs injured with live bacteria. Am. J. Respir. Crit. Care Med. 2013;187:751–760. doi: 10.1164/rccm.201206-0990OC.
    1. Ryan J.M., Barry F.P., Murphy J.M., Mahon B.P. Mesenchymal stem cells avoid allogeneic rejection. J. Inflamm. 2005;2:8. doi: 10.1186/1476-9255-2-8.
    1. Matthay M.A., Calfee C.S., Zhuo H., Thompson B.T., Wilson J.G., Levitt J.E., Rogers A.J., Gotts J.E., Wiener-Kronish J.P., Bajwa E.K., et al. Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): A randomised phase 2a safety trial. Lancet Respir. Med. 2019;7:154–162. doi: 10.1016/S2213-2600(18)30418-1.
    1. Lalu M.M., McIntyre L., Pugliese C., Fergusson D., Winston B.W., Marshall J.C., Granton J., Stewart D.J., Canadian Critical Care Trials G. Safety of cell therapy with mesenchymal stromal cells (SafeCell): A systematic review and meta-analysis of clinical trials. PLoS ONE. 2012;7:e47559. doi: 10.1371/journal.pone.0047559.
    1. Gorman E., Shankar-Hari M., Hopkins P., Tunnicliffe W.S., Perkins G.D., Silversides J., McGuigan P., Krasnodembskaya A., Jackson C., Boyle R., et al. Repair of acute respiratory distress syndrome by stromal cell administration (REALIST) trial: A phase 1 trial. EClinicalMedicine. 2021;41:101167. doi: 10.1016/j.eclinm.2021.101167.
    1. Lee J.W., Fang X., Gupta N., Serikov V., Matthay M.A. Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung. Proc. Natl. Acad. Sci. USA. 2009;106:16357–16362. doi: 10.1073/pnas.0907996106.
    1. Viget N.B., Guery B.P., Ader F., Neviere R., Alfandari S., Creuzy C., Roussel-Delvallez M., Foucher C., Mason C.M., Beaucaire G., et al. Keratinocyte growth factor protects against Pseudomonas aeruginosa-induced lung injury. Am. J. Physiol. Lung Cell Mol. Physiol. 2000;279:L1199–L1209. doi: 10.1152/ajplung.2000.279.6.L1199.
    1. Welsh D.A., Summer W.R., Dobard E.P., Nelson S., Mason C.M. Keratinocyte growth factor prevents ventilator-induced lung injury in an ex vivo rat model. Am. J. Respir. Crit. Care Med. 2000;162:1081–1086. doi: 10.1164/ajrccm.162.3.9908099.
    1. Mason C.M., Guery B.P., Summer W.R., Nelson S. Keratinocyte growth factor attenuates lung leak induced by alpha-naphthylthiourea in rats. Crit. Care Med. 1996;24:925–931. doi: 10.1097/00003246-199606000-00009.
    1. McAuley D.F., Curley G.F., Hamid U.I., Laffey J.G., Abbott J., McKenna D.H., Fang X., Matthay M.A., Lee J.W. Clinical grade allogeneic human mesenchymal stem cells restore alveolar fluid clearance in human lungs rejected for transplantation. Am. J. Physiol. Lung Cell Mol. Physiol. 2014;306:L809–L815. doi: 10.1152/ajplung.00358.2013.
    1. Fang X., Abbott J., Cheng L., Colby J.K., Lee J.W., Levy B.D., Matthay M.A. Human Mesenchymal Stem (Stromal) Cells Promote the Resolution of Acute Lung Injury in Part through Lipoxin A4. J. Immunol. 2015;195:875–881. doi: 10.4049/jimmunol.1500244.
    1. Mordant P., Nakajima D., Kalaf R., Iskender I., Maahs L., Behrens P., Coutinho R., Iyer R.K., Davies J.E., Cypel M., et al. Mesenchymal stem cell treatment is associated with decreased perfusate concentration of interleukin-8 during ex vivo perfusion of donor lungs after 18-hour preservation. J. Heart Lung Transpl. 2016;35:1245–1254. doi: 10.1016/j.healun.2016.04.017.
    1. Nakajima D., Watanabe Y., Ohsumi A., Pipkin M., Chen M., Mordant P., Kanou T., Saito T., Lam R., Coutinho R., et al. Mesenchymal stromal cell therapy during ex vivo lung perfusion ameliorates ischemia-reperfusion injury in lung transplantation. J. Heart Lung Transpl. 2019;38:1214–1223. doi: 10.1016/j.healun.2019.07.006.
    1. Pacienza N., Santa-Cruz D., Malvicini R., Robledo O., Lemus-Larralde G., Bertolotti A., Marcos M., Yannarelli G. Mesenchymal Stem Cell Therapy Facilitates Donor Lung Preservation by Reducing Oxidative Damage during Ischemia. Stem Cells Int. 2019;2019:8089215. doi: 10.1155/2019/8089215.
    1. La Francesca S., Ting A.E., Sakamoto J., Rhudy J., Bonenfant N.R., Borg Z.D., Cruz F.F., Goodwin M., Lehman N.A., Taggart J.M., et al. Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: An initial pilot and feasibility study. Transpl. Res. 2014;3:19. doi: 10.1186/2047-1440-3-19.
    1. Martens A., Ordies S., Vanaudenaerde B.M., Verleden S.E., Vos R., Van Raemdonck D.E., Verleden G.M., Roobrouck V.D., Claes S., Schols D., et al. Immunoregulatory effects of multipotent adult progenitor cells in a porcine ex vivo lung perfusion model. Stem. Cell Res. Ther. 2017;8:159. doi: 10.1186/s13287-017-0603-5.
    1. Nykanen A.I., Mariscal A., Duong A., Estrada C., Ali A., Hough O., Sage A., Chao B.T., Chen M., Gokhale H., et al. Engineered mesenchymal stromal cell therapy during human lung ex vivo lung perfusion is compromised by acidic lung microenvironment. Mol. Ther. Methods Clin. Dev. 2021;23:184–197. doi: 10.1016/j.omtm.2021.05.018.
    1. Mohamed M.S. Mesenchymal stem cells transplantation during ex vivo lung perfusion. J. Heart Lung Transpl. 2017;36:243. doi: 10.1016/j.healun.2016.10.010.
    1. Baksh D., Yao R., Tuan R.S. Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells. 2007;25:1384–1392. doi: 10.1634/stemcells.2006-0709.
    1. Laffey J.G., Matthay M.A. Fifty Years of Research in ARDS. Cell-based Therapy for Acute Respiratory Distress Syndrome. Biology and Potential Therapeutic Value. Am. J. Respir Crit Care Med. 2017;196:266–273. doi: 10.1164/rccm.201701-0107CP.
    1. Wick K.D., Leligdowicz A., Zhuo H., Ware L.B., Matthay M.A. Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS. JCI Insight. 2021;6 doi: 10.1172/jci.insight.148983.
    1. Thery C., Witwer K.W., Aikawa E., Alcaraz M.J., Anderson J.D., Andriantsitohaina R., Antoniou A., Arab T., Archer F., Atkin-Smith G.K., et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell Vesicles. 2018;7:1535750. doi: 10.1080/20013078.2018.1535750.
    1. Kronstadt S.M., Pottash A.E., Levy D., Wang S., Chao W., Jay S.M. Therapeutic Potential of Extracellular Vesicles for Sepsis Treatment. Adv. Ther. 2021;4:2000259. doi: 10.1002/adtp.202000259.
    1. Stone M.L., Zhao Y., Robert Smith J., Weiss M.L., Kron I.L., Laubach V.E., Sharma A.K. Mesenchymal stromal cell-derived extracellular vesicles attenuate lung ischemia-reperfusion injury and enhance reconditioning of donor lungs after circulatory death. Respir. Res. 2017;18:212. doi: 10.1186/s12931-017-0704-9.
    1. Gennai S., Monsel A., Hao Q., Park J., Matthay M.A., Lee J.W. Microvesicles Derived From Human Mesenchymal Stem Cells Restore Alveolar Fluid Clearance in Human Lungs Rejected for Transplantation. Am. J. Transpl. 2015;15:2404–2412. doi: 10.1111/ajt.13271.
    1. Zhu Y.G., Feng X.M., Abbott J., Fang X.H., Hao Q., Monsel A., Qu J.M., Matthay M.A., Lee J.W. Human mesenchymal stem cell microvesicles for treatment of Escherichia coli endotoxin-induced acute lung injury in mice. Stem Cells. 2014;32:116–125. doi: 10.1002/stem.1504.
    1. Zhu Y., Wang Y., Zhao B., Niu X., Hu B., Li Q., Zhang J., Ding J., Chen Y., Wang Y. Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis. Stem Cell Res. Ther. 2017;8:64. doi: 10.1186/s13287-017-0510-9.
    1. Elsharkasy O.M., Nordin J.Z., Hagey D.W., de Jong O.G., Schiffelers R.M., Andaloussi S.E., Vader P. Extracellular vesicles as drug delivery systems: Why and how? Adv. Drug Deliv. Rev. 2020;159:332–343. doi: 10.1016/j.addr.2020.04.004.
    1. Lonati C., Bassani G.A., Brambilla D., Leonardi P., Carlin A., Maggioni M., Zanella A., Dondossola D., Fonsato V., Grange C., et al. Mesenchymal stem cell-derived extracellular vesicles improve the molecular phenotype of isolated rat lungs during ischemia/reperfusion injury. J. Heart Lung Transpl.. 2019;38:1306–1316. doi: 10.1016/j.healun.2019.08.016.
    1. Varkouhi A.K., Jerkic M., Ormesher L., Gagnon S., Goyal S., Rabani R., Masterson C., Spring C., Chen P.Z., Gu F.X., et al. Extracellular Vesicles from Interferon-gamma-primed Human Umbilical Cord Mesenchymal Stromal Cells Reduce Escherichia coli-induced Acute Lung Injury in Rats. Anesthesiology. 2019;130:778–790. doi: 10.1097/ALN.0000000000002655.
    1. Park J., Kim S., Lim H., Liu A., Hu S., Lee J., Zhuo H., Hao Q., Matthay M.A., Lee J.W. Therapeutic effects of human mesenchymal stem cell microvesicles in an ex vivo perfused human lung injured with severe E. coli pneumonia. Thorax. 2019;74:43–50. doi: 10.1136/thoraxjnl-2018-211576.
    1. Miceli V., Bertani A., Chinnici C.M., Bulati M., Pampalone M., Amico G., Carcione C., Schmelzer E., Gerlach J.C., Conaldi P.G. Conditioned Medium from Human Amnion-Derived Mesenchymal Stromal/Stem Cells Attenuating the Effects of Cold Ischemia-Reperfusion Injury in an In Vitro Model Using Human Alveolar Epithelial Cells. Int. J. Mol. Sci. 2021;22:510. doi: 10.3390/ijms22020510.
    1. Huang R., Qin C., Wang J., Hu Y., Zheng G., Qiu G., Ge M., Tao H., Shu Q., Xu J. Differential effects of extracellular vesicles from aging and young mesenchymal stem cells in acute lung injury. Aging. 2019;11:7996–8014. doi: 10.18632/aging.102314.
    1. Gimona M., Pachler K., Laner-Plamberger S., Schallmoser K., Rohde E. Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use. Int. J. Mol. Sci. 2017;18:1190. doi: 10.3390/ijms18061190.
    1. Vallabhajosyula P., Korutla L., Habertheuer A., Reddy S., Schaufler C., Lasky J., Diamond J., Cantu E., 3rd Ex Vivo Lung Perfusion Model to Study Pulmonary Tissue Extracellular Microvesicle Profiles. Ann. Thorac. Surg. 2017;103:1758–1766. doi: 10.1016/j.athoracsur.2016.11.074.
    1. Gruda M.C., Ruggeberg K.G., O’Sullivan P., Guliashvili T., Scheirer A.R., Golobish T.D., Capponi V.J., Chan P.P. Broad adsorption of sepsis-related PAMP and DAMP molecules, mycotoxins, and cytokines from whole blood using CytoSorb(R) sorbent porous polymer beads. PLoS ONE. 2018;13:e0191676. doi: 10.1371/journal.pone.0191676.
    1. Nemeth E., Kovacs E., Racz K., Soltesz A., Szigeti S., Kiss N., Csikos G., Koritsanszky K.B., Berzsenyi V., Trembickij G., et al. Impact of intraoperative cytokine adsorption on outcome of patients undergoing orthotopic heart transplantation-an observational study. Clin. Transpl. 2018;32:e13211. doi: 10.1111/ctr.13211.
    1. Ferdinand J.R., Hosgood S.A., Moore T., Ferro A., Ward C.J., Castro-Dopico T., Nicholson M.L., Clatworthy M.R. Cytokine absorption during human kidney perfusion reduces delayed graft function-associated inflammatory gene signature. Am. J. Transpl. 2021;21:2188–2199. doi: 10.1111/ajt.16371.
    1. Schadler D., Pausch C., Heise D., Meier-Hellmann A., Brederlau J., Weiler N., Marx G., Putensen C., Spies C., Jorres A., et al. The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial. PLoS ONE. 2017;12:e0187015. doi: 10.1371/journal.pone.0187015.
    1. Rieder M., Wengenmayer T., Staudacher D., Duerschmied D., Supady A. Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation. Crit. Care. 2020;24:435. doi: 10.1186/s13054-020-03130-y.
    1. Popescu M., Dima S., David C., Tudor A., Simionescu M., Tomescu D. Standard renal replacement therapy combined with hemoadsorption in the treatment of critically ill septic patients. Ther. Apher. Dial. 2021;25:663–670. doi: 10.1111/1744-9987.13612.
    1. Schittek G.A., Zoidl P., Eichinger M., Orlob S., Simonis H., Rief M., Metnitz P., Fellinger T., Soukup J. Adsorption therapy in critically ill with septic shock and acute kidney injury: A retrospective and prospective cohort study. Ann. Intensive Care. 2020;10:154. doi: 10.1186/s13613-020-00772-7.
    1. Friesecke S., Stecher S.S., Gross S., Felix S.B., Nierhaus A. Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: A prospective single-center study. J. Artif. Organs. 2017;20:252–259. doi: 10.1007/s10047-017-0967-4.
    1. Butt Y., Kurdowska A., Allen T.C. Acute Lung Injury: A Clinical and Molecular Review. Arch. Pathol. Lab. Med. 2016;140:345–350. doi: 10.5858/arpa.2015-0519-RA.
    1. Meduri G.U., Headley S., Kohler G., Stentz F., Tolley E., Umberger R., Leeper K. Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time. Chest. 1995;107:1062–1073. doi: 10.1378/chest.107.4.1062.
    1. Agrawal A., Zhuo H., Brady S., Levitt J., Steingrub J., Siegel M.D., Soto G., Peterson M.W., Chesnutt M.S., Matthay M.A., et al. Pathogenetic and predictive value of biomarkers in patients with ALI and lower severity of illness: Results from two clinical trials. Am. J. Physiol. Lung Cell Mol. Physiol. 2012;303:L634–L639. doi: 10.1152/ajplung.00195.2012.
    1. Kakishita T., Oto T., Hori S., Miyoshi K., Otani S., Yamamoto S., Waki N., Yoshida O., Okazaki M., Yamane M., et al. Suppression of inflammatory cytokines during ex vivo lung perfusion with an adsorbent membrane. Ann. Thorac. Surg. 2010;89:1773–1779. doi: 10.1016/j.athoracsur.2010.02.077.
    1. Iskender I., Arni S., Maeyashiki T., Citak N., Sauer M., Rodriguez J.M., Frauenfelder T., Opitz I., Weder W., Inci I. Perfusate adsorption during ex vivo lung perfusion improves early post-transplant lung function. J. Thorac. Cardiovasc. Surg. 2021;161:e109–e121. doi: 10.1016/j.jtcvs.2019.12.128.
    1. Iskender I., Cosgun T., Arni S., Trinkwitz M., Fehlings S., Yamada Y., Cesarovic N., Yu K., Frauenfelder T., Jungraithmayr W., et al. Cytokine filtration modulates pulmonary metabolism and edema formation during ex vivo lung perfusion. J. Heart Lung Transpl. 2017 doi: 10.1016/j.healun.2017.05.021.

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