Sustained function of genetically modified porcine lungs in an ex vivo model of pulmonary xenotransplantation

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dc.contributor.authorWestall, G.
dc.contributor.authorLevvey, B.
dc.contributor.authorSalvaris, E.
dc.contributor.authorGooi, J.
dc.contributor.authorMarasco, S.
dc.contributor.authorRosenfeldt, F.
dc.contributor.authorEgan, C.
dc.contributor.authorMcEgan, R.
dc.contributor.authorMennen, M.
dc.contributor.authorRussell, P.
dc.contributor.authorRobson, S.
dc.contributor.authorNottle, M.
dc.contributor.authorDwyer, K.
dc.contributor.authorSnell, G.
dc.contributor.authorCowan, P.
dc.date.issued2013
dc.description.abstractBACKGROUND Xenotransplantation could provide a solution to the donor shortage that is currently the major barrier to solid-organ transplantation. The ability to breed pigs with multiple genetic modifications provides a unique opportunity to explore the immunologic challenges of pulmonary xenotransplantation. METHODS Explanted lungs from wild-type and 3 groups of genetically modified pigs were studied: (i) α1,3-galactosyltransferase gene knockout (GTKO); (ii) GTKO pigs expressing the human complementary regulatory proteins CD55 and CD59 (GTKO/CD55-59); and (iii) GTKO pigs expressing both CD55-59 and CD39 (GTKO/CD55-59/CD39). The physiologic, immunologic and histologic properties of porcine lungs were evaluated on an ex vivo rig after perfusion with human blood. Results Lungs from genetically modified pigs demonstrated stable pulmonary vascular resistance and better oxygenation of the perfusate, and survived longer than wild-type lungs. Physiologic function was inversely correlated with the degree of platelet sequestration into the xenograft. Despite superior physiologic profiles, lungs from genetically modified pigs still showed evidence of intravascular thrombosis and coagulopathy after perfusion with human blood. CONCLUSIONS The ability to breed pigs with multiple genetic modifications, and to evaluate lung physiology and histology in real-time on an ex vivo rig, represent significant advances toward better understanding the challenges inherent to pulmonary xenotransplantation.
dc.description.statementofresponsibilityGlen P. Westall, Browyn J. Levvey, Evelyn Salvaris, Julian Gooi, Sylvana Marasco, Frank Rosenfeldt, Chris Egan, Robin McEgan, Mark Mennen, Prue Russell, Simon C. Robson, Mark B. Nottle, Karen M. Dwyer, Greg I. Snell, Peter J. Cowan
dc.identifier.citationJournal of Heart and Lung Transplantation, 2013; 32(11):1123-1130
dc.identifier.doi10.1016/j.healun.2013.07.001
dc.identifier.issn1053-2498
dc.identifier.issn1557-3117
dc.identifier.orcidNottle, M. [0000-0001-7625-5542]
dc.identifier.urihttp://hdl.handle.net/2440/81548
dc.language.isoen
dc.publisherElsevier Science Inc
dc.rights© 2013 International Society for Heart and Lung Transplantation.
dc.source.urihttps://doi.org/10.1016/j.healun.2013.07.001
dc.subjectex vivo lung perfusion
dc.subjectGal knockout
dc.subjectgenetically engineered
dc.subjecthyperacute rejection
dc.subjectlung
dc.subjectswine
dc.subjectxenotransplantation
dc.titleSustained function of genetically modified porcine lungs in an ex vivo model of pulmonary xenotransplantation
dc.typeJournal article
pubs.publication-statusPublished

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