Mesenchymal stem cells improve the outcomes of liver recipients via regulating CD4+ T helper cytokines in rats

Yang, Yang; Shen, Zhongyang; Wu, Bin; Yin, Mingli; Zhang, Boya; Song, Hongli

doi:10.1016/s1499-3872(16)60085-1

Cited by 12 publications

(23 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BMMSCs can alleviate hepatic IRI, reduce hepatocyte damage, accelerate liver regeneration, participate in the anti-inflammatory response, and regulate immunity (Wu et al 2016 ; Yang et al 2016a ). We have shown that, when combined with NMP, BMMSCs can colonize DCD liver and have an effect, so we used BMMSCs plus NMP to observe the influence on DCD liver quality and investigate its mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…Microcirculatory disorders are the determinants of liver damage; acute liver injury, IRI, and inflammation can cause liver microcirculatory disorders (Vollmar and Menger 2009 ; Gracia-Sancho et al 2019 ). Bone marrow mesenchymal stem cells (BMMSCs) are a class of non-hematopoietic stem cells derived from stromal cells that can regulate immunity, participate in the anti-inflammatory response, and secrete cytokines (Yang et al 2016a , b ; Zheng et al 2018 ; Marquez-Curtis et al 2015 ; Sassoli et al 2018 ), which can inhibit the macrophage-mediated inflammatory response (Li et al 2016 ) and improve IRI (Chu et al 2019 ). BMMSC transplantation can reduce hepatic IRI and inhibit hepatocyte apoptosis in transplanted livers (Wu et al 2016 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bone marrow mesenchymal stem cells combine with normothermic machine perfusion to improve rat donor liver quality—the important role of hepatic microcirculation in donation after circulatory death

et al. 2020

Self Cite

View full text Add to dashboard Cite

Donation after circulatory death (DCD) can expand the donor pool effectively. A gap remains in outcome between DCD livers and living donor livers, warranting improved DCD liver quality and urgent resolution. Bone marrow mesenchymal stem cells (BMMSCs) can regulate immunity, participate in the anti-inflammatory response, and secrete cytokines. We investigated the effect of BMMSCs combined with normothermic machine perfusion (NMP) on DCD liver quality, and the role of microcirculation therein. Rat thoracic aortas were clipped to obtain DCD livers, and a rat NMP system was established. The DCD livers were grouped by preservation method: normal, static cold storage (SCS), NMP (P), and BMMSCs plus NMP (BP); storage time was up to 8 h. Liver function in outflow perfusate was detected by biochemical methods; liver tissue histopathology was observed by hematoxylin-eosin staining; hepatocyte ultrastructure was observed by transmission electron microscopy; hepatocyte apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling; liver microcirculation-related indicators were detected by immunofluorescence, immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay. Compared with SCS, P and BP significantly improved liver function and liver histological damage, reduced hepatocyte apoptosis, and repaired hepatocyte mitochondrial damage after 6 h in vitro. BP also significantly inhibited intrahepatic macrophage activation and intercellular adhesion, improved endothelial damage, and significantly improved endothelin 1-nitric oxide balance and microcirculation perfusion. In conclusion, BP can improve DCD liver microcirculation and quality. The mechanism may be the improvement of improve hepatic sinusoidal endothelial injury and microcirculation perfusion by inhibiting macrophage activation and intercellular adhesion.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bone marrow mesenchymal stem cells combine with normothermic machine perfusion to improve rat donor liver quality—the important role of hepatic microcirculation in donation after circulatory death

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Reduction of the PVP and improvement of hepatic venous perfusion are important to improve liver function after RLT[39]. BMMSCs have tissue repair, regulation of inflammation, and immune response functions, and have protective effects on transplanted livers[22,27,41,42]. To solve the problem that BMMSCs have low activity in damaged tissue[43], and have a short survival time[22,24,44,45], adenovirus-transduced BMMSCs expressing HO-1 were used to study their protective effects on transplanted livers, sinusoidal microcirculation, and energy metabolism after RLT.…”

Section: Discussionmentioning

confidence: 99%

Effects of heme oxygenase-1-modified bone marrow mesenchymal stem cells on microcirculation and energy metabolism following liver transplantation

Liu

Shen

Wang

et al. 2017

WJG

Self Cite

View full text Add to dashboard Cite

AIMTo investigate the effects of heme oxygenase-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) on the microcirculation and energy metabolism of hepatic sinusoids following reduced-size liver transplantation (RLT) in a rat model.METHODSBMMSCs were isolated and cultured in vitro using an adherent method, and then transduced with HO-1-bearing recombinant adenovirus to construct HO-1/BMMSCs. A rat acute rejection model following 50% RLT was established using a two-cuff technique. Recipients were divided into three groups based on the treatment received: normal saline (NS), BMMSCs and HO-1/BMMSCs. Liver function was examined at six time points. The levels of endothelin-1 (ET-1), endothelial nitric-oxide synthase (eNOS), inducible nitric-oxide synthase (iNOS), nitric oxide (NO), and hyaluronic acid (HA) were detected using an enzyme-linked immunosorbent assay. The portal vein pressure (PVP) was detected by Power Lab ML880. The expressions of ET-1, iNOS, eNOS, and von Willebrand factor (vWF) protein in the transplanted liver were detected using immunohistochemistry and Western blotting. ATPase in the transplanted liver was detected by chemical colorimetry, and the ultrastructural changes were observed under a transmission electron microscope.RESULTSHO-1/BMMSCs could alleviate the pathological changes and rejection activity index of the transplanted liver, and improve the liver function of rats following 50% RLT, with statistically significant differences compared with those of the NS group and BMMSCs group (P < 0.05). In term of the microcirculation of hepatic sinusoids: The PVP on POD7 decreased significantly in the HO-1/BMMSCs and BMMSCs groups compared with that of the NS group (P < 0.01); HO-1/BMMSCs could inhibit the expressions of ET-1 and iNOS, increase the expressions of eNOS and inhibit amounts of NO production, and maintain the equilibrium of ET-1/NO (P < 0.05); and HO-1/BMMSCs increased the expression of vWF in hepatic sinusoidal endothelial cells (SECs), and promoted the degradation of HA, compared with those of the NS group and BMMSCs group (P < 0.05). In term of the energy metabolism of the transplanted liver, HO-1/BMMSCs repaired the damaged mitochondria, and improved the activity of mitochondrial aspartate aminotransferase (ASTm) and ATPase, compared with the other two groups (P <0.05).CONCLUSIONHO-1/BMMSCs can improve the microcirculation of hepatic sinusoids significantly, and recover the energy metabolism of damaged hepatocytes in rats following RLT, thus protecting the transplanted liver.

show abstract

“…So we will propose a wider range of cell lines in vitro and relevant animal models in vivo for future studies. The mechanism will be more complex in vivo, and many immune cells may be involved in it (Yang et al, , ).…”

Section: Discussionmentioning

confidence: 99%

Effect of heme oxygenase‐1 transduced bone marrow mesenchymal stem cells on damaged intestinal epithelial cells in vitro

Cao

Zheng

et al. 2017

Cell Biology International

Self Cite

View full text Add to dashboard Cite

In this study, we explored the effects of mesenchymal stem cells (MSCs) from bone marrow overexpressing heme oxygenase-1 (HO-1) on the damaged human intestinal epithelial barrier in vitro. Rat MSCs were isolated from bone marrow and transduced with rat HO-1 recombinant adenovirus (HO-MSCs) for stable expression of HO-1. Colorectal adenocarinoma 2 (Caco2) cells were treated with tumor necrosis factor-a (TNF-a) to establish a damaged colon epithelial model. Damaged Caco2 were cocultured with MSCs, Ad-MSCs, Ad-HO þ MSCs or HO-MSCs. mRNA and protein expression of Zona occludens-1 (ZO-1) and human HO-1 and the release of cytokines were measured. ZO-1 and human HO-1 in Caco2 were significantly decreased after treatment with TNF-a; and this effect was reduced when coculture with MSCs from bone marrow. Expression of ZO-1 was not significantly affected by Caco2 treatment with TNF-a, Ad-HO, and MSCs. In contrast, ZO-1 and human HO-1 increased significantly when the damaged Caco2 was treated with HO-MSCs. HO-MSCs showed the strongest effect on the expression of ZO-1 in colon epithelial cells. Coculture with HO-MSCs showed the most significant effects on reducing the expression of IL-2, IL-6, IFN-g and increasing the expression of IL-10. HO-MSCs protected the intestinal epithelial barrier, in which endogenous HO-1 was involved. HO-MSCs play an important role in the repair process by reducing the release of inflammatory cytokines and increasing the release of anti-inflammatory factors. These results suggested that HO-MSCs from bone marrow were more effective in repairing the damaged intestinal epithelial barrier, and the effectiveness of MSCs was improved by HO-1 gene transduction, which provides favorable support for the application of stem cell therapy in the intestinal diseases.

show abstract

Mesenchymal stem cells improve the outcomes of liver recipients via regulating CD4+ T helper cytokines in rats

Cited by 12 publications

References 44 publications

Bone marrow mesenchymal stem cells combine with normothermic machine perfusion to improve rat donor liver quality—the important role of hepatic microcirculation in donation after circulatory death

Bone marrow mesenchymal stem cells combine with normothermic machine perfusion to improve rat donor liver quality—the important role of hepatic microcirculation in donation after circulatory death

Effects of heme oxygenase-1-modified bone marrow mesenchymal stem cells on microcirculation and energy metabolism following liver transplantation

Effect of heme oxygenase‐1 transduced bone marrow mesenchymal stem cells on damaged intestinal epithelial cells in vitro

Contact Info

Product

Resources

About