Normothermic machine perfusion using an air/oxygen mixer: reconditioning a marginal donor liver

Abstract Background Liver transplantation (LT) is required in many end-stage liver diseases. Donation after cardiac death (DCD) livers are often used, and treatment of acute rejection (ACR) requires the use of immunosuppressive drugs that are associated with complications. Bone marrow mesenchymal stem cells (BMMSCs) are used in treatment following LT; however, they have limitations, including low colonization in the liver. An optimized BMMSC application method is required to suppress ACR. Methods BMMSCs were isolated and modified with the heme oxygenase 1 (HO-1) gene. HO-1/BMMSCs were perfused into donor liver in vitro using a normothermic machine perfusion (NMP) system, followed by LT into rats. The severity of ACR was evaluated based on liver histopathology. Gene chip technology was used to detect differential gene expression, and flow cytometry to analyze changes in natural killer (NK) T cells. Results NMP induced BMMSCs to colonize the donor liver during in vitro preservation. The survival of HO-1/BMMSCs in liver grafts was significantly longer than that of unmodified BMMSCs. When the donor liver contained HO-1/BMMSCs, the local immunosuppressive effect was improved and prolonged, ACR was controlled, and survival time was significantly prolonged. The application of HO-1/BMMSCs reduced the number of NKT cells in liver grafts, increased the expression of NKT cell co-inhibitory receptors, and reduced NKT cell expression of interferon-γ. Conclusions NK cell and CD8+ T cell activation was inhibited by application of HO-1/BMMSCs, which reduced ACR of transplanted liver. This approach could be developed to enhance the success rate of LT.

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Continuous Normothermic Machine Perfusion for Renovation of Extended Criteria Donor Livers Without Recooling in Liver Transplantation: A Pilot Experience

Frontiers in Surgery ◽

10.3389/fsurg.2021.638090 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zhitao Chen ◽

Xitao Hong ◽

Shanzhou Huang ◽

Tielong Wang ◽

Yihao Ma ◽

...

Keyword(s):

Acute Hepatic Failure ◽

Meld Score ◽

Decompensated Cirrhosis ◽

Machine Perfusion ◽

Donor Liver ◽

Extended Criteria Donor ◽

Allograft Function ◽

Normothermic Machine Perfusion ◽

End Stage ◽

Early Allograft Dysfunction

Background: Ischemia injury affects the recovery of liver allograft function. We propose a novel technique aimed at avoiding a second ischemic injury: transplanting an extended criteria donor (ECD) liver directly under normothermic machine perfusion (NMP) without recooling. We studied two cases to evaluate the efficacy and safety of this technique.Methods: The perioperative characteristics and postoperative outcomes of two recipients of ECD livers were analyzed. Both transplantations were performed with continuous normothermic machine perfusion without recooling.Result: In case 1, the cause of donor death was anoxia, and the donor liver had hypernatremia before procurement. The recipient was diagnosed with decompensated cirrhosis. His model for end-stage liver disease (MELD) score was 38. In case 2, the donor liver was from a donor after cardiac death (DCD), and the donor had elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. The recipient was diagnosed with acute hepatic failure. His MELD score was 35. Both donor livers were maintained under NMP and then transplanted without recooling. The peak ALT and AST levels after surgery were 452 and 770 U/L in case 1 and 100 and 592 U/L in case 2. Neither early allograft dysfunction (EAD) nor primary graft non-function (PNF) was present in these two cases.Conclusion: In conclusion, our results demonstrate that continuous NMP without recooling is efficacious and safe for LT with extended criteria donor livers. Further investigations of this technique will be performed to confirm these promising results.

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Experimental perfusion device for preservation of donor’s liver

Grekov s Bulletin of Surgery ◽

10.24884/0042-4625-2017-176-3-88-92 ◽

2017 ◽

Vol 176 (3) ◽

pp. 88-92

Author(s):

S. F. Bagnenko ◽

O. N. Reznik ◽

A. E. Skvortsov ◽

A. V. Lopota ◽

N. A. Gryaznov ◽

...

Keyword(s):

Biochemical Parameters ◽

Warm Ischemia ◽

Central Research ◽

Machine Perfusion ◽

Clinical Tests ◽

Donor Liver ◽

Porcine Liver ◽

Design Institute ◽

Normothermic Perfusion ◽

Normothermic Machine Perfusion

OBJECTIVE. The authors aimed to develop complex perfusion medical device in order to successfully maintain viability of donor liver until transplantation. MATERIAL AND METHODS. Experimental perfusion device for normothermic perfusion donor’s liver was developed and tested in the Central Research and Experimental-design Institute of Robotics and Technical Cybernetics. RESULTS. The pre-clinical tests were performed on porcine liver. It was demonstrated that normothermic machine perfusion could restore liver function after 30 minutes of warm ischemia time and provide normalization of biochemical parameters of organ functioning.

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Assessment of deceased brain dead donor liver grafts via normothermic machine perfusion: Lactate clearance time threshold can be safely extended to six hours

Liver Transplantation ◽

10.1002/lt.26317 ◽

2021 ◽

Author(s):

Angus Hann ◽

Hanns Lembach ◽

Anisa Nutu ◽

Hynek Mergental ◽

John L Isaac ◽

...

Keyword(s):

Lactate Clearance ◽

Machine Perfusion ◽

Clearance Time ◽

Donor Liver ◽

Time Threshold ◽

Normothermic Machine Perfusion ◽

Brain Dead ◽

Brain Dead Donor

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HO-1/Bmmscs Perfusion Using a Normothermic Machine Perfusion System Reduces the Acute Rejection of DCD Liver Transplantation by Regulating NKT Cell Co-Inhibitory Receptors

10.21203/rs.3.rs-380793/v1 ◽

2021 ◽

Author(s):

Huan Cao ◽

Longlong Wu ◽

Xuan Tian ◽

Weiping Zheng ◽

Mengshu Yuan ◽

...

Keyword(s):

Liver Transplantation ◽

Acute Rejection ◽

Survival Time ◽

Nkt Cells ◽

Machine Perfusion ◽

Donor Liver ◽

Nkt Cell ◽

Normothermic Machine Perfusion ◽

Ifn Γ

Abstract Background: Liver transplantation (LT) represents the most effective treatment for many end-stage liver diseases. While donation after cardiac death (DCD) donor livers are used due to organ shortage, acute rejection (ACR) remains an important risk factor affecting the survival of recipients following transplantation. Although immunosuppressive agents can be used, they are associated with complications. Bone marrow mesenchymal stem cells (BMMSCs) are used in the treatment of organ transplantation; however, there is limited colonization in the target organs and a short survival time following BMMSCs application. Thus, an optimized BMMSCs application method is required to suppress immune rejection and promote the long-term survival of allogeneic liver transplant recipients. Methods: BMMSCs were isolated and modified with heme oxygenase 1 (HO-1) gene. HO-1/BMMSCs were perfused into the donor liver in vitro using a normothermic machine perfusion (NMP) system, followed by LT. The severity of ACR was evaluated based on the liver histopathology. Gene chip technology was used to detect differential gene expression, and the flow cytometry was used to analyze changes in natural killer (NK) T cells. Results: NMP can induce BMMSCs to colonize the donor liver during in vitro preservation, and the survival of HO-1/BMMSCs in the liver grafts was significantly longer than that of BMMSCs. When the donor liver contained HO-1/BMMSCs, the ACR is obviously controlled, and the survival time was significantly prolonged. The application of HO-1/BMMSCs reduces the number of NKT cells in the liver grafts, increases the expression of the NKT cell co-inhibitory receptors, and reduces the level of NKT cell expression of IFN-γ. Thus, NK cell and CD8+ T cell activation was inhibited, which reduced acute of rejection of the transplanted liver. Conclusions: The NMP system preserves the DCD donor liver in vitro, and also allows large quantities of BMMSCs to colonize the liver. HO-1-modified BMMSCs are able to improve and prolong the local immunosuppressive effect of BMMSCs following transplantation by reducing the number of NKT cells and up-regulating NKT cell co-inhibitory receptor expression. This results in the transmission of inhibitory signals to NKT cells, reduced NKT cell IFN-γ levels, and the inhibition of ACR.

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