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

Glen P. Westall, Browyn J. Levvey, Evelyn J 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

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17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1123-1130
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume32
Issue number11
DOIs
Publication statusPublished - Nov 2013
Externally publishedYes

Keywords

  • ex vivo lung perfusion
  • Gal knockout
  • genetically engineered
  • hyperacute rejection
  • lung
  • swine
  • xenotransplantation

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