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Coagulation and the xenograft endothelium
Author(s) -
Cowan Peter J.
Publication year - 2007
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2006.00368.x
Subject(s) - thrombotic microangiopathy , thrombomodulin , xenotransplantation , endothelium , immunology , coagulation , thrombosis , transplantation , medicine , endothelial stem cell , cancer research , biology , pathology , platelet , thrombin , in vitro , biochemistry , disease
Acute humoral rejection remains the major barrier to long‐term pig‐to‐primate xenograft survival, and microvascular thrombosis is a critical element of the rejection process. It appears that persistent endothelial cell activation and injury, by even low levels of anti‐graft antibodies, eventually overwhelm the cellular anticoagulant defences and promote the development of thrombotic microangiopathy. Porcine endothelium may be particularly vulnerable because of cross‐species molecular incompatibilities affecting the function of thrombomodulin and possibly TFPI. Recent data from small animal models suggest that transgenic overexpression of anti‐thrombotic molecules on xenograft endothelium is capable of inhibiting intravascular thrombosis and preventing acute humoral rejection. In conjunction with existing genetic modifications (e.g. Gal KO, hDAF), this is a promising strategy to move xenotransplantation to the clinic.