Hypothermic Oxygenated Perfusion (HOPE) downregulates the immune response in a rat model of liver transplantation.
- Schlegel A *Laboratory of the Swiss HPB and Transplant Center, Department of Surgery, University Hospital Zurich, Switzerland †Hospital Paul Brousse, Université Paris Sud, Paris, France.
- Kron P
- Graf R
- Clavien PA
- Dutkowski P
- 2014-09-23
Published in:
- Annals of surgery. - 2014
Animals
Disease Models, Animal
Down-Regulation
Graft Rejection
Hypothermia, Induced
Kupffer Cells
Liver Transplantation
Oxygen
Perfusion
Rats
Rats, Inbred Lew
Reperfusion Injury
Survival Rate
Tacrolimus
English
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.
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.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1097/SLA.0000000000000941
- PMID 25243553
- Persistent URL
- https://sonar.ch/global/documents/263416
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