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Hypothermic Oxygenated Perfusion (HOPE) downregulates the immune response in a rat model of liver transplantation


Schlegel, Andrea; Kron, Philipp; Graf, Rolf; Clavien, Pierre-Alain; Dutkowski, Philipp (2014). Hypothermic Oxygenated Perfusion (HOPE) downregulates the immune response in a rat model of liver transplantation. Annals of Surgery, 260(5):931-937.

Abstract

OBJECTIVE: To evaluate the impact of a novel oxygenated perfusion approach on rejection after orthotopic liver transplantation (OLT).
BACKGROUND: Hypothermic oxygenated perfusion (HOPE) was designed to prevent graft failure after OLT. One of the mechanisms is downregulation of Kupffer cells (in situ macrophages). We, therefore, designed experiments to test the effects of HOPE on the immune response in an allogeneic rodent model of nonarterialized OLT.
METHODS: Livers from Lewis rats were transplanted into Brown Norway rats to induce liver rejection in untreated recipients within 4 weeks. Next, Brown Norway recipients were treated with tacrolimus (1 mg/kg), whereas in a third group, liver grafts from Lewis rats underwent HOPE or deoxygenated machine perfusion for 1 hour before implantation, but recipients received no immunosuppression. In a last step, low-dose tacrolimus treatment (0.3 mg/kg) was assessed with and without HOPE.
RESULTS: Allogeneic OLT without immunosuppression led to death within 3 weeks after nonarterialized OLT due to severe acute rejection. Full-dose tacrolimus prevented rejection, whereas low-dose tacrolimus led to graft fibrosis within 4 weeks. HOPE treatment without immunosuppression also protected from lethal rejection. The combination of low-dose tacrolimus and 1-hour HOPE resulted in 100% survival within 4 weeks without any signs of rejection.
CONCLUSIONS: We demonstrate that allograft treatment by HOPE not only protects against preservation injury but also impressively downregulates the immune system, blunting the alloimmune response. Therefore, HOPE may offer many beneficial effects, not only to rescue marginal grafts but also by preventing rejection and the need for immunosuppression.

Abstract

OBJECTIVE: To evaluate the impact of a novel oxygenated perfusion approach on rejection after orthotopic liver transplantation (OLT).
BACKGROUND: Hypothermic oxygenated perfusion (HOPE) was designed to prevent graft failure after OLT. One of the mechanisms is downregulation of Kupffer cells (in situ macrophages). We, therefore, designed experiments to test the effects of HOPE on the immune response in an allogeneic rodent model of nonarterialized OLT.
METHODS: Livers from Lewis rats were transplanted into Brown Norway rats to induce liver rejection in untreated recipients within 4 weeks. Next, Brown Norway recipients were treated with tacrolimus (1 mg/kg), whereas in a third group, liver grafts from Lewis rats underwent HOPE or deoxygenated machine perfusion for 1 hour before implantation, but recipients received no immunosuppression. In a last step, low-dose tacrolimus treatment (0.3 mg/kg) was assessed with and without HOPE.
RESULTS: Allogeneic OLT without immunosuppression led to death within 3 weeks after nonarterialized OLT due to severe acute rejection. Full-dose tacrolimus prevented rejection, whereas low-dose tacrolimus led to graft fibrosis within 4 weeks. HOPE treatment without immunosuppression also protected from lethal rejection. The combination of low-dose tacrolimus and 1-hour HOPE resulted in 100% survival within 4 weeks without any signs of rejection.
CONCLUSIONS: We demonstrate that allograft treatment by HOPE not only protects against preservation injury but also impressively downregulates the immune system, blunting the alloimmune response. Therefore, HOPE may offer many beneficial effects, not only to rescue marginal grafts but also by preventing rejection and the need for immunosuppression.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Visceral and Transplantation Surgery
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:November 2014
Deposited On:08 Jan 2015 11:12
Last Modified:14 Feb 2018 22:28
Publisher:Lippincott Williams & Wilkins
ISSN:0003-4932
OA Status:Green
Publisher DOI:https://doi.org/10.1097/SLA.0000000000000941
PubMed ID:25243553

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