BACKGROUND: Recent years have brought dramatic progress in the field of xenotransplantation, with the development of transgenic swine and various other means of overcoming the rejection mediated by xenoreactive antibodies. Although progress has been rapid with kidney and heart xenografts, progress with pulmonary xenografts has lagged behind. Recent findings have suggested that donor pulmonary intravascular macrophages may play a critical role in the hyperacute dysfunction of pulmonary xenografts. METHODS: The function of pulmonary xenografts from pigs depleted of pulmonary intravascular macrophages was compared with the function of xenografts from normal pigs. RESULTS: Pulmonary xenografts from pigs from which pulmonary intravascular macrophages were depleted survived (23.5+/-0.9 hours) about five times longer than normal (macrophage sufficient) xenografts (4.4+/-1.41 hours) (P< 0.0001). At 21 hours post-reperfusion, the left pulmonary arterial flow was 225.0+/-34 ml/min in lungs depleted of pulmonary intravascular macrophages, whereas all normal xenografts had failed. CONCLUSIONS: These findings indicate that donor macrophages play a critical role in pulmonary xenograft dysfunction. This finding has broad implications for xenotransplantation, suggesting that porcine macrophages might pose a barrier to the engraftment and function of a variety of porcine organ xenografts.
BACKGROUND: Recent years have brought dramatic progress in the field of xenotransplantation, with the development of transgenic swine and various other means of overcoming the rejection mediated by xenoreactive antibodies. Although progress has been rapid with kidney and heart xenografts, progress with pulmonary xenografts has lagged behind. Recent findings have suggested that donor pulmonary intravascular macrophages may play a critical role in the hyperacute dysfunction of pulmonary xenografts. METHODS: The function of pulmonary xenografts from pigs depleted of pulmonary intravascular macrophages was compared with the function of xenografts from normal pigs. RESULTS: Pulmonary xenografts from pigs from which pulmonary intravascular macrophages were depleted survived (23.5+/-0.9 hours) about five times longer than normal (macrophage sufficient) xenografts (4.4+/-1.41 hours) (P< 0.0001). At 21 hours post-reperfusion, the left pulmonary arterial flow was 225.0+/-34 ml/min in lungs depleted of pulmonary intravascular macrophages, whereas all normal xenografts had failed. CONCLUSIONS: These findings indicate that donor macrophages play a critical role in pulmonary xenograft dysfunction. This finding has broad implications for xenotransplantation, suggesting that porcine macrophages might pose a barrier to the engraftment and function of a variety of porcine organ xenografts.
Authors: Bao-Ngoc H Nguyen; Agnes M Azimzadeh; Carsten Schroeder; Thomas Buddensick; Tianshu Zhang; Amal Laaris; Megan Cochrane; Henk-Jan Schuurman; David H Sachs; James S Allan; Richard N Pierson Journal: Xenotransplantation Date: 2011 Mar-Apr Impact factor: 3.907
Authors: David K C Cooper; Burcin Ekser; Christopher Burlak; Mohamed Ezzelarab; Hidetaka Hara; Leela Paris; A Joseph Tector; Carol Phelps; Agnes M Azimzadeh; David Ayares; Simon C Robson; Richard N Pierson Journal: Xenotransplantation Date: 2012 May-Jun Impact factor: 3.907
Authors: Donald G Harris; Kevin J Quinn; Siamak Dahi; Lars Burdorf; Agnes M Azimzadeh; Richard N Pierson Journal: Xenotransplantation Date: 2014-07-05 Impact factor: 3.907
Authors: Donald G Harris; Kevin J Quinn; Beth M French; Evan Schwartz; Elizabeth Kang; Siamak Dahi; Carol J Phelps; David L Ayares; Lars Burdorf; Agnes M Azimzadeh; Richard N Pierson Journal: Xenotransplantation Date: 2014-12-02 Impact factor: 3.907