Composite tissue vasculopathy and degeneration following multiple episodes of acute rejection in reconstructive transplantation

J. V. Unadkat, S. Schneeberger, E. H. Horibe, C. Goldbach, M. G. Solari, K. M. Washington, V. S. Gorantla, G. M. Cooper, A. W. Thomson, W. P. Andrew Lee

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

Transplant vasculopathy has not been systematically investigated in composite tissue allotransplantation (CTA). The impact of multiple acute rejections (ARs) on long-term graft outcomes in reconstructive transplantation remains unknown. This study in a rat hind-limb allotransplantation model systematically analyzes vasculopathy and tissue-specific pathological changes secondary to multiple AR episodes. LEW rats were transplanted with BN rat hind limbs and treated as follows: Group 1 (Iso): isografts. Group 2 (CsA): Cyclosporine (CsA) qd; Group 3 (mult AR): CsA and dexamethasone only when AR was observed. No AR was observed in Groups 1 and 2. Multiple AR were observed in Group 3, and each episode was completely reversed (clinically) with pulsed CsA + dexamethasone treatment. Group 3 animals demonstrated significant vascular lesions along with skin and muscle atrophy, upregulation of profibrotic gene expression and fibrosis when compared to Groups 1 and 2. In addition, allograft bone was sclerotic, weak and prone to malunion and nonunion. Interestingly, vasculopathy was a late finding, whereas muscle atrophy with macrophage infiltration was seen early, after only a few AR episodes. Taken together, multiple AR episodes lead to vasculopathy and tissue-specific pathology in CTA. This is the first evidence of 'composite tissue vasculopathy and degeneration (CTVD)' in CTA.

Original languageEnglish (US)
Pages (from-to)251-261
Number of pages11
JournalAmerican Journal of Transplantation
Volume10
Issue number2
DOIs
StatePublished - Feb 1 2010
Externally publishedYes

Keywords

  • Chronic allograft dysfunction
  • Chronic allograft rejection
  • Chronic graft deterioration
  • Chronic rejection
  • Composite tissue allograft
  • Composite tissue transplantation
  • Face transplantation
  • Graft fibrosis
  • Graft vessel disease
  • Hand transplant

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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    Unadkat, J. V., Schneeberger, S., Horibe, E. H., Goldbach, C., Solari, M. G., Washington, K. M., Gorantla, V. S., Cooper, G. M., Thomson, A. W., & Andrew Lee, W. P. (2010). Composite tissue vasculopathy and degeneration following multiple episodes of acute rejection in reconstructive transplantation. American Journal of Transplantation, 10(2), 251-261. https://doi.org/10.1111/j.1600-6143.2009.02941.x