scholarly journals HO-1/BMMSC perfusion using a normothermic machine perfusion system reduces the acute rejection of DCD liver transplantation by regulating NKT cell co-inhibitory receptors in rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Huan Cao ◽  
Longlong Wu ◽  
Xuan Tian ◽  
Weiping Zheng ◽  
Mengshu Yuan ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Acute Rejection ◽  
T Cell Activation ◽  
Heme Oxygenase 1 ◽  
Machine Perfusion ◽  
Inhibitory Receptors ◽  
Donor Liver ◽  
Nkt Cell ◽  
Normothermic Machine Perfusion

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.

scholarly journals 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

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.

scholarly journals Heme Oxygenase-1-Modified Bone Marrow Mesenchymal Stem Cells Combined with Normothermic Machine Perfusion Repairs Bile Duct Injury in a Rat Model of DCD Liver Transplantation via Activation of Peribiliary Glands through the Wnt Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Xuan Tian ◽  
Huan Cao ◽  
Longlong Wu ◽  
Weiping Zheng ◽  
Mengshu Yuan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Liver Transplantation ◽  
Bile Duct ◽  
Progenitor Cells ◽  
Bile Duct Injury ◽  
Heme Oxygenase 1 ◽  
Machine Perfusion ◽  
Marrow Mesenchymal Stem Cells ◽  
Normothermic Machine Perfusion ◽  
Peribiliary Glands

Livers from donors after circulatory death (DCD) are inevitably exposed to a longer warm ischemic period, which might increase the incidence of postoperative bile duct complications. Bone marrow mesenchymal stem cells (BMMSCs) have tissue repair properties. The present study was aimed at exploring the repair effect of heme oxygenase-1- (HO-1-) modified BMMSCs (HO-1/BMMSCs) combined with normothermic machine perfusion (NMP) on bile duct injury after DCD liver transplantation and at revealing the underlying mechanisms. Rat livers were exposed to in situ warm ischemia for 30 min; then, NMP was performed through the portal vein for 4 h with BMMSCs, HO-1/BMMSCs, or neither before implantation. Obvious bile duct histological damage and liver functional damage were observed postoperatively. In the group treated with HO-1/BMMSCs combined with NMP (HBP group), liver functions and bile duct histology were improved; meanwhile, cell apoptosis was reduced and cell proliferation was active. A large number of regenerative cells appeared at the injured site, and the defective bile duct epithelium was restored. Dilatation of peribiliary glands (PBGs), proliferation of PBG cells, high expression of vascular endothelial growth factor (VEGF), and increased proportion of bile duct progenitor cells with stem/progenitor cells biomarkers were observed. Blocking Wnt signaling significantly inhibited the repair effect of HO-1/BMMSCs on bile duct injury. In conclusion, HO-1/BMMSCs combined with NMP were relevant to the activation of biliary progenitor cells in PBGs which repaired bile duct injury in DCD liver transplantation via the Wnt signaling pathway. Proliferation and differentiation of PBG cells were involved in the renewal of the injured biliary epithelium.

Recent advances in liver transplantation

2021 ◽  
pp. flgastro-2020-101425
Author(s):  
N Thomas Burke ◽  
James B Maurice ◽  
David Nasralla ◽  
Jonathan Potts ◽  
Rachel Westbrook
Keyword(s):  
Liver Transplantation ◽  
Survival Rates ◽  
Machine Perfusion ◽  
Allocation System ◽  
Life Saving ◽  
Opt Out ◽  
Normothermic Machine Perfusion ◽  
Marginal Grafts ◽  
Legislative Changes ◽  
The Uk

Liver transplant is a life-saving treatment with 1-year and 5-year survival rates of 90% and 70%, respectively. However, organ demand continues to exceed supply, such that many patients will die waiting for an available organ. This article reviews for the general gastroenterologist the latest developments in the field to reduce waiting list mortality and maximise utilisation of available organs. The main areas covered include legislative changes in organ donation and the new ‘opt-out’ systems being rolled out in the UK, normothermic machine perfusion to optimise marginal grafts, a new national allocation system to maximise benefit from each organ and developments in patient ‘prehabilitation’ before listing. Current areas of research interest, such as immunosuppression withdrawal, are also summarised.

scholarly journals Normothermic Machine Perfusion Using an Air/Oxygen Mixer: Reconditioning a Marginal Donor Liver

HPB ◽  
2019 ◽  
Vol 21 ◽  
pp. S776-S777
Author(s):  
F. Di Francesco ◽  
P. Bonsignore ◽  
G. Martucci ◽  
D. Pagano ◽  
D. Cintorino ◽  
...  
Keyword(s):  
Machine Perfusion ◽  
Donor Liver ◽  
Marginal Donor ◽  
Normothermic Machine Perfusion
Sign in / Sign up

Export Citation Format

Share Document