Composite tissue allotransplantation: development of a preclinical model in nonhuman primates.

Abstract:

BACKGROUND:Composite tissue allotransplantation (CTA) has been recently introduced as a potential treatment for tissue loss secondary to burns, injuries, or resections. However, the optimal strategies to prevent CTA rejection remain undefined. Presently, no CTA model exists to evaluate human-specific immunosuppressants or the relative immunogenicity of all CTA tissues. METHODS:We established a NHP CTA model utilizing a sensate osteomyocutaneous radial forearm flap that avoids functional impairment even in the case of graft loss. The model was evaluated in19 monkeys that underwent auto- or allotransplantation, with or without subtherapeutic immunosuppression to temporarily characterize rejection. RESULTS:Autografts showed no evidence of rejection. Nonimmunosuppressed allografts were rapidly rejected showing a perivenular T-cell infiltrate. This was associated with subsequent alloantibody formation and led to graft thrombosis without prominent dermal infiltration. Subtherapeutically immunosuppressed animals also developed alloantibody and rejected in a delayed fashion exhibiting a marked dermal lymphocytic infiltrate similar in magnitude and distribution to previously reported human cases. CONCLUSION:Our NHP model for CTA is well tolerated by NHPs, results in allosensitization, is responsive to immunosuppression, allows for the evaluation of CTA histology and can be used for the systematic preclinical evaluation of therapeutic maneuvers to improve allograft survival.

journal_name

Transplantation

journal_title

Transplantation

authors

Cendales LC,Xu H,Bacher J,Eckhaus MA,Kleiner DE,Kirk AD

doi

10.1097/01.tp.0000183292.57349.27

subject

Has Abstract

pub_date

2005-11-27 00:00:00

pages

1447-54

issue

10

eissn

0041-1337

issn

1534-6080

pii

00007890-200511270-00016

journal_volume

80

pub_type

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