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Type: Journal article
Title: Sustained function of genetically modified porcine lungs in an ex vivo model of pulmonary xenotransplantation
Author: Westall, G.
Levvey, B.
Salvaris, E.
Gooi, J.
Marasco, S.
Rosenfeldt, F.
Egan, C.
McEgan, R.
Mennen, M.
Russell, P.
Robson, S.
Nottle, M.
Dwyer, K.
Snell, G.
Cowan, P.
Citation: Journal of Heart and Lung Transplantation, 2013; 32(11):1123-1130
Publisher: Elsevier Science Inc
Issue Date: 2013
ISSN: 1053-2498
Statement of
Glen 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
Abstract: BACKGROUND 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.
Keywords: ex vivo lung perfusion; Gal knockout; genetically engineered; hyperacute rejection; lung; swine; xenotransplantation
Rights: © 2013 International Society for Heart and Lung Transplantation.
RMID: 0020132559
DOI: 10.1016/j.healun.2013.07.001
Appears in Collections:Obstetrics and Gynaecology publications

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