Composite tissue allotransplantation: Development of a preclinical model in nonhuman primates

Linda C. Cendales*, He Xu, John Bacher, Michael A. Eckhaus, David E. Kleiner, Allan D. Kirk

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


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 in 19 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.

Original languageEnglish
Pages (from-to)1447-1454
Number of pages8
Issue number10
StatePublished - Nov 2005
Externally publishedYes


  • Allograft
  • Animal model
  • Composite tissue allotransplantation
  • Nonhuman primates
  • Transplantation


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