Coagulation and the xenograft endothelium.

Abstract:

: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.

journal_name

Xenotransplantation

journal_title

Xenotransplantation

authors

Cowan PJ

doi

10.1111/j.1399-3089.2006.00368.x

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

7-12

issue

1

eissn

0908-665X

issn

1399-3089

pii

XEN368

journal_volume

14

pub_type

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