- 作者：Glen P. Westall ; Browyn J. Levvey ; Evelyn Salvaris ; Julian Gooi ; Sylvana Marasco ; Frank Rosenfeldt ; Chris Egan ; Robin McEgan ; CCP ; Mark Mennen ; Prue Russell ; Simon C. Robson ; Mark B. Nottle ; Karen M. Dwyer ; Greg I. Snell ; Peter J. Cowan
- 关键词：xenotransplantation ; ex vivo lung perfusion ; genetically engineered ; lung ; swine ; Gal knockout ; hyperacute rejection
- 刊名：The Journal of Heart and Lung Transplantation
- 出版年：2013
- 出版时间：November, 2013
- 年：2013
- 卷：32
- 期：11
- 页码：1123-1130
- 全文大小：5843 K
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) ¦Á1,3-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.