The coagulation barrier in xenotransplantation: incompatibilities and strategies to overcome them.

Abstract:

PURPOSE OF REVIEW:Dysregulated coagulation is now recognized as a major contributor to graft loss in xenotransplantation. This review summarizes recent data on putative mechanisms of pathogenic coagulation in xenotransplantation and discusses progress on strategies to overcome them. RECENT FINDINGS:Evidence continues to grow that the primary cause of failure of pig cardiac and renal xenografts is probably antibody-mediated injury to the endothelium, leading to development of microvascular thrombosis. Several factors that may exacerbate the problem will remain, even in the absence of a humoral response. These include molecular incompatibilities that affect the control of coagulation - in particular the failure of pig thrombomodulin to activate the primate protein C pathway - and platelet reactivity. Expression of anticoagulant and antiplatelet molecules within the graft is a potential solution that has been successfully tested in rodent models and will soon be applied to the pig-to-primate model. This strategy, in parallel with physical methods such as encasing islets in a protective layer, also holds promise for reducing the thrombogenicity of pig islet xenografts. SUMMARY:Thrombosis is a barrier to long-term survival and function of porcine xenografts, which may eventually be overcome by various combinations of genetic and physical manipulation.

authors

Cowan PJ,d'Apice AJ

doi

10.1097/MOT.0b013e3282f63c74

subject

Has Abstract

pub_date

2008-04-01 00:00:00

pages

178-83

issue

2

eissn

1087-2418

issn

1531-7013

pii

00075200-200804000-00011

journal_volume

13

pub_type

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