Heme Oxygenase-1-Modified Bone Marrow Mesenchymal Stem Cells Perfusion Using a Normothermic Machine Perfusion System Reduces the Acute Rejection of Liver Transplantation by Regulating Natural Killer T Cell Co-Inhibitory Receptors

2021 ◽  
Author(s):  
Huan Cao ◽  
Longlong Wu ◽  
Xuan Tian ◽  
Weiping Zheng ◽  
Mengshu Yuan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Liver Transplantation ◽  
Heme Oxygenase 1 ◽  
Machine Perfusion ◽  
Perfusion System ◽  
Natural Killer T Cell ◽  
Marrow Mesenchymal Stem Cells ◽  
Normothermic Machine Perfusion ◽  
Killer T Cell

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.

scholarly journals Improvement of Liver Transplantation Outcome by Heme Oxygenase-1-Transduced Bone Marrow Mesenchymal Stem Cells in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Bin Wu ◽  
Hong-Li Song ◽  
Yang Yang ◽  
Ming-Li Yin ◽  
Bo-Ya Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Liver Transplantation ◽  
Mesenchymal Stem Cells ◽  
Heme Oxygenase ◽  
Transforming Growth Factor ◽  
The Other ◽  
Heme Oxygenase 1 ◽  
Immunomodulatory Effects ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMMSCs) exert immunosuppressive activity in transplantation, and heme oxygenase-1 (HO-1) enhances their immunomodulatory effects. The aim of this study was to determine whether HO-1-transduced BMMSCs (HO-1/MSCs) improve rat liver transplantation (LTx) outcomes. Orthotopic LTx rejection models were treated with HO-1/MSCs, BMMSCs, HO-1, or normal saline, respectively. Our results showed a significant improvement in survival rates in the HO-1/BMMSCs group compared to the control groups. At all time points, liver function marker levels in the HO-1/MSCs group were significantly lower than in the other three groups; on POD 1, 7, and 14, the degree of rejection and apoptotic cells was significantly less in the HO-1/MSCs group than in the other three groups. Interleukin- (IL-) 10 and transforming growth factor-βlevels were significantly increased, while IL-2, IL-6, IL-17, IL-23, tumor necrosis factor-α, and interferon-γlevels were significantly decreased in the HO-1/MSCs group when compared to the other groups. Splenocyte Tregs were significantly increased by HO-1/MSCs compared with controls on POD 3, 5, 7, 10, 14, and 28. Summarily, we provide evidence that HO-1/MSCs improved allogeneic LTx outcomes by attenuating inflammatory responses and acute cellular rejection, as well as enhanced immunomodulatory effects compared with BMMSCs.

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