Transgenic swine lungs expressing human cd59 are protected from injury in a pig-to- human model of xenotransplantation David M. Kulick, MDa, Christopher.

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Presentation transcript:

Transgenic swine lungs expressing human cd59 are protected from injury in a pig-to- human model of xenotransplantation David M. Kulick, MDa, Christopher T. Salerno, MDa, Agustin P. Dalmasso, MDb,c, Soon J. Park, MDa, Manuel Guzman Paz, MDc, William L. Fodor, PhDd, R.Morton Bolman, MDa The Journal of Thoracic and Cardiovascular Surgery Volume 119, Issue 4, Pages 690-699 (April 2000) DOI: 10.1016/S0022-5223(00)70003-1 Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 1 PVR and pulmonary compliance for control (♦) and transgenic (♢) lungs perfused with human blood (mean ± standard deviation; P = .018 for PVR; P = .001 for pulmonary compliance transgenic vs control; analysis of variance). Time 0 represents measurements obtained during the first 15 seconds of the experiment. In this and subsequent illustrations, n = 6 for the control group and n = 5 for the transgenic group. The Journal of Thoracic and Cardiovascular Surgery 2000 119, 690-699DOI: (10.1016/S0022-5223(00)70003-1) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 2 ΔAVO2 and A-a O2 gradient for control (♦) and transgenic (♢) lungs perfused with human blood (mean ± standard deviation). The Journal of Thoracic and Cardiovascular Surgery 2000 119, 690-699DOI: (10.1016/S0022-5223(00)70003-1) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 3 IgG and IgM xenoreactive natural antibody from control (♦) and transgenic (♢) lungs perfused with human blood. Levels are expressed as a percentage of values before perfusion. Data are reported as mean ± standard deviation. The Journal of Thoracic and Cardiovascular Surgery 2000 119, 690-699DOI: (10.1016/S0022-5223(00)70003-1) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 4 Plasma levels of total complement hemolytic activity (CH50) in control (♦) and transgenic (♢) lungs perfused with human blood. Data are reported as mean ± standard deviation for percentage decline in CH50 compared with preperfusion levels. The Journal of Thoracic and Cardiovascular Surgery 2000 119, 690-699DOI: (10.1016/S0022-5223(00)70003-1) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 5 Plasma levels of complement fragment C3a and soluble complement complex SC5b9 from control (♦) and transgenic (♢) lungs perfused with human blood. Data are reported as mean ± standard deviation (**P < .01, t test). The Journal of Thoracic and Cardiovascular Surgery 2000 119, 690-699DOI: (10.1016/S0022-5223(00)70003-1) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 6 Histologic features of pulmonary parenchymal sections obtained after the completion of the perfusion experiments with human blood (Hematoxylin and eosin stain; original magnification, ×40). Control porcine lung tissues reveal interstitial, perivascular, peribronchial hemorrhage, and neutrophil infiltration. Transgenic porcine lung tissues demonstrate reduced interstitial hemorrhage, interalveolar septal edema and congestion, and preserved pulmonary tissue architecture. The Journal of Thoracic and Cardiovascular Surgery 2000 119, 690-699DOI: (10.1016/S0022-5223(00)70003-1) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 7 Immunofluorescence analysis of porcine lungs perfused with human blood reveals equivalent deposition of C3 for both control and transgenic lungs. Terminal complement component C9 deposition was reduced in transgenic lungs as compared with control lungs. Preperfusion right porcine lung specimens revealed strong expression of hCD59 in transgenic lung parenchyma and no hCD59 reactivity in control lung parenchyma. The Journal of Thoracic and Cardiovascular Surgery 2000 119, 690-699DOI: (10.1016/S0022-5223(00)70003-1) Copyright © 2000 Mosby, Inc. Terms and Conditions