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Local gene therapy with indoleamine 2,3-dioxygenase protects against development of transplant vasculopathy in chronic kidney transplant dysfunction

Vavrincova-Yaghi, D., Deelman, L., van Goor, H., Seelen, M. A., Vavrinec, P., Kema, I. P., Gomolcak, P., Benigni, A., Henning, R. H. & Sandovici, M., Aug-2016, In : Gene Therapy. 23, 11, p. 797-806 10 p.

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  • Local gene therapy with indoleamine 2,3-dioxygenase protects against development

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DOI

Chronic transplant dysfunction (CTD) is the primary cause of late allograft loss in kidney transplantation. Indoleamine 2,3-dioxygenase (IDO) is involved in fetomaternal tolerance and IDO gene therapy inhibits acute rejection following kidney transplantation. The aim of this study is to investigate whether gene therapy with IDO is able to attenuate CTD. Transplantation was performed in a rat Dark-Agouti to Wistar-Furth CTD model. Donor kidneys were incubated either with an adenovirus carrying IDO gene, a control adenovirus or saline. During the first 10 days recipients received low-dose cyclosporine. Body weight, blood pressure, serum creatinine and proteinuria were measured every 2 weeks. Rats were killed after 12 weeks. IDO had a striking beneficial effect on transplant vasculopathy at week 12. It also significantly improved body weight gain; it reduced blood pressure and decreased proteinuria during the follow-up. However, it did not affect the kidney function. In addition, IDO therapy significantly decreased the number of graft-infiltrating macrophages at week 12. The messenger RNA levels of forkhead box p3 and transforming grow factor-beta were elevated in the IDO treated group at week 12. Here we show for first time a clear beneficial effect of local IDO gene therapy especially on transplant vasculopathy in a rat model of renal CTD.

Original languageEnglish
Pages (from-to)797-806
Number of pages10
JournalGene Therapy
Volume23
Issue number11
Early online date4-Aug-2016
Publication statusPublished - Aug-2016

    Keywords

  • CHRONIC ALLOGRAFT NEPHROPATHY, REGULATORY T-CELLS, TRYPTOPHAN CATABOLISM, DENDRITIC CELLS, TRANSGENE EXPRESSION, 2,3 DIOXYGENASE, RGD MOTIF, HI LOOP, ADENOVIRUS, REJECTION

ID: 35192045