Portal donor-specific blood transfusion and mycophenolate mofetil allow steroid avoidance and tacrolimus dose reduction with sustained levels of chimerism in a pig model of intestinal transplantation

Transplantation
Rainer W G GruessnerA C Gruessner

Abstract

In a pig model of intestinal transplantation, we previously showed that hepatic conditioning through portal donor-specific blood transfusion (pDSBT), high-dose tacrolimus (TAC), and steroids prevented rejection and increased survival Our current study tests a protocol of pDSBT, short-term mycophenolate mofetil (MMF), and low-dose TAC to eliminate the use of steroids, reduce TAC dosage, and increase the level of chimerism in the peripheral blood. Four groups of outbred, mixed lymphocyte culture (MLC)-reactive pigs underwent bowel transplants and pDSBT. Immunosuppression (group 1, high-dose TAC and steroids; group 2, low-dose TAC and MMF; group 3, low-dose TAC, MMF, and aminoguanidine; group 4, low-dose TAC, MMF, and arginine) was discontinued after 28 days. RNA was extracted from intestinal graft and native liver biopsies for cytokine measurements. Chimerism levels were determined using a Q-PCR analysis. Pig survival and death rates due to rejection did not significantly differ between the four groups. Chimerism levels determined by Q-PCR analysis were not different until day 28. After discontinuation of immunosuppression, we noted a trend (P = 0.15) toward higher mean chimerism levels on day 60 for groups 2, 3, and 4 (9%) vs. g...Continue Reading

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Citations

Apr 9, 2005·European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes·J A Diaz-Peromingo, A Gonzalez-Quintela
Sep 24, 2004·Transplant Immunology·Jacques Pirenne, Masaru Kawai
Nov 26, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·M AvsarG Warnecke
Jul 30, 2016·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Dimitra KotsougianiAllen T Bishop
Jan 18, 2017·Transplant International : Official Journal of the European Society for Organ Transplantation·Wiebke SommerGregor Warnecke
Oct 11, 2016·Cellular & Molecular Immunology·Rita DiehlJohannes Boltze

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