gms | German Medical Science

125. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

22. - 25.04.2008, Berlin

Mesenchymal stem cells induce long-term acceptance of solid organ allografts by indoleamine 2,3-dioxygenase

Meeting Abstract

  • corresponding author F.C. Popp - Klinik und Poliklinik für Chirurgie, Universität Regensburg, Regensburg, Deutschland
  • E. Eggenhofer - Klinik und Poliklinik für Chirurgie, Universität Regensburg, Regensburg, Deutschland
  • P. Renner - Klinik und Poliklinik für Chirurgie, Universität Regensburg, Regensburg, Deutschland
  • P. Slowik - Klinik und Poliklinik für Chirurgie, Universität Regensburg, Regensburg, Deutschland
  • S.A. Lang - Klinik und Poliklinik für Chirurgie, Universität Regensburg, Regensburg, Deutschland
  • E.K. Geissler - Klinik und Poliklinik für Chirurgie, Universität Regensburg, Regensburg, Deutschland
  • P. Piso - Klinik und Poliklinik für Chirurgie, Universität Regensburg, Regensburg, Deutschland
  • H.J. Schlitt - Klinik und Poliklinik für Chirurgie, Universität Regensburg, Regensburg, Deutschland
  • M.H. Dahlke - Klinik und Poliklinik für Chirurgie, Universität Regensburg, Regensburg, Deutschland

Deutsche Gesellschaft für Chirurgie. 125. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 22.-25.04.2008. Düsseldorf: German Medical Science GMS Publishing House; 2008. Doc08dgch8788

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgch2008/08dgch432.shtml

Veröffentlicht: 16. April 2008

© 2008 Popp et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: The induction of tolerance towards allogeneic solid organ grafts is one of the major goals in transplantation medicine. Mesenchymal stem cells (MSC) inhibit the proliferation of T cells in vitro, and thus are promising candidate cells to promote acceptance of transplanted organs in vivo. Such novel approaches of tolerance induction are needed since, to date, graft acceptance can only be achieved through life-long treatment with unspecific immunosuppressants, which are associated with opportunistic infections and malignancies caused by their mechanism of action.

Materials and methods: Heterotopic heart transplantation was performed using LEW rats as donors and ACI rats as recipients. 2*10^6 MSC were injected into the tail vein four days in advance. In some groups injections were performed immediately after heart transplantation with an additional injection on day 3. Mycophenolate mofetil (MMF) was injected intraperitoneally at a dosage of 20 mg/kg BW/d from day 0 to day 7 in designated experiments. Some animals received 10 mg 1 methyl tryptophan twice a day subcutaneously from day 0 to day 7. Graft rejection time was defined as the day at which no cardiac contractions were palpable.

Results: In our current work, we demonstrate that donor-derived MSC induce long-term allograft acceptance in a rat heart transplantation model, when concurrently applied with a short course of low-dose mycophenolate mofetil (MMF). The tolerogenic effect of MSC was mediated by the expression of indoleamine 2,3-dioxygenase (IDO) because blocking of IDO with 1-methyl tryptophan (1-MT) abrogated graft acceptance. In this respect, MSC-mediated tolerance is different from donor leukocyte-mediated tolerance. The application of donor leucocytes also induced graft acceptance in our model, but not through IDO, since blocking of IDO did not result in graft rejection.

Conclusion: In summary, we demonstrate that MSC constitute a promising tool for the induction of non-responsiveness in solid organ transplantation that warrants further investigation in clinical studies.