ORIGINAL ARTICLES   

Minerva Chirurgica 2006 April;61(2):85-94

Copyright © 2006 EDIZIONI MINERVA MEDICA

language: Italian

Immunomodulation after combined spleen and kidney transplantation in swine

Rademacher J. ^{1, 2}, Cansolino L. ², Crespi S. ¹, Lenti L. M. ¹, Lillo E. ¹, Tubazio I. ¹, Oldani O. ¹, Passalia L. ², Maestri M. ^{2, 3}, Gaspari A. ¹, Dionigi P. ^{2, 3}

¹ Università degli Studi di Pavia 2 Dipartimento di Scienze Chirurgiche Rianimatorie, Riabilitative e dei Trapianti d’organo Laboratorio di Chirurgia Sperimentale, Pavia 3 Istituto di Chirurgia Epatopancreatica IRCCS Policlinico S. Matteo, Pavia

Aim. Organ transplantation is the most effective treatment for several degenerative end-stage diseases. While the mainstream immunosuppression can achieve satisfactory results, the therapy has either side effects and flaws. The golden target to reach should be a stable tolerance with the transplanted organ accepted without a long term drug administration. Recent studies demonstrated a tolerogenic effect of spleen cells. Aim of this study is to evaluate a model of combined spleen and whole organ transplantation in a significant preclinical setting in swine.
Methods. Twenty-five outbred Landrace/Large-White swine underwent combined spleen/kidney transplantation (SKTx). The experiments were stratified into 3 groups per randomization. Group 1 (N=7) received kidney transplantation (KTx) alone with no immunosuppressive treatment. Group 2 (N=9) had a combined KTx and whole graft spleen Tx. Group 3 (N=9) had KTx and spleen cells (DST), injected through the portal vein. Renal lab tests were collected to evaluate the onset of rejection. Survivals were evaluated as well. The end-point of the study was at onset of kidney failure or at the limit of 60 postoperative day (POD) in non-rejecting animals. Tissue samples were collected to evaluate grade and severity of rejection.
Results. Controls died from kidney failure within 10th POD. Group 2 and 3, had a delayed renal graft rejection and an overall prolonged graft survival. Whole graft and spleen cells injection share this effect, while spleen administration through the portal route proved a superior effect, which is significant compared to controls (Kaplan Meier survival analysis P<0.05).
Conclusion. These results, from a non immunosuppressed setting, suggest that spleen plays a key role as an immunomodulatory organ.