The Effect of Vascular Endothelial Growth Factor on Bone Marrow Mesenchymal Stem Cell Engraftment in Rat Fibrotic Liver upon Transplantation
Background. According to existing related experiments and research reports, stem cell transplantation therapy has been shown to have a positive effect on the recovery of liver fibrosis/cirrhosis, but for some reason, this therapy still cannot be widely used in clinical work. One of the reasons that...
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Wiley
2019-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2019/5310202 |
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| author | Ke Yuan Chunyou Lai Lingling Wei Tianhang Feng Qinyan Yang Tianying Zhang Tao Lan Yutong Yao Guangming Xiang Xiaolun Huang |
| author_facet | Ke Yuan Chunyou Lai Lingling Wei Tianhang Feng Qinyan Yang Tianying Zhang Tao Lan Yutong Yao Guangming Xiang Xiaolun Huang |
| author_sort | Ke Yuan |
| collection | DOAJ |
| description | Background. According to existing related experiments and research reports, stem cell transplantation therapy has been shown to have a positive effect on the recovery of liver fibrosis/cirrhosis, but for some reason, this therapy still cannot be widely used in clinical work. One of the reasons that cannot be ignored is the low quantity of exogenous stem cells transplanted into the liver in vivo. Thus, we investigated whether the use of the vascular endothelial growth factor (VEGF) can increase the number of stem cell transplants and improve the efficacy of stem cell transplantation therapy. Methods. Using a Sprague-Dawley rat liver fibrosis model, we transplanted into fibrosis liver allograft bone marrow mesenchymal stem cells (BMSCs) which were labelled with chlormethylbenzamido-1,1-dioctadecyl-3,3,3′3′-tetramethylin-docarbocyamine (CM-DiI) or injected VEGF adenovirus solution through the tail vein or conducted the above two operations simultaneously. The cell surface receptor profile of BMSC was examined by flow cytometry and immunofluorescence staining. Hepatic sinusoidal vascular leakage was measured with Evan’s blue dye assay. Paraffin section staining, immunofluorescent staining, RT-qPCR (quantitative reverse transcription polymerase chain reaction), and Western blot were used to evaluate hepatic pathological changes and physiology function. Result. The in vivo study indicated that, comparing with other groups of rats, the rats with combined treatment of BMSC transplantation and VEGF injection exhibited obvious reduction in liver fibrosis. Evan’s blue dye assay suggests that after injecting with VEGF adenovirus solution, the rat’s hepatic sinusoidal permeability would be increased. We confirmed the expression of very late antigen-4 (VLA4, integrin α4β1) on rat BMSCs and the elevated expression of vascular adhesion molecule-1 (VCAM-1) in the hepatic sinusoidal endothelial cells. In addition, the analysis of CM-DiI-labeled BMSCs showed that the BMSC+VEGF group exhibited better cell engraftment and that the engrafted cells were mainly distributed in the hepatic parenchyma. Furthermore, compared with the other situation, it is best to reconstitute the liver secretion and regeneration function of rats after combined application of VEGF and BMSC. Conclusion. We showed that VEGF promotes the engraftment of BMSCs in liver fibrosis, enhances liver regeneration, and improves liver function. These outcomes may be related to the increasing hepatic sinusoidal endothelium permeability and VCAM-1-increased expression. |
| format | Article |
| id | doaj-art-5a43b2c6377547aea186bd6ecf3bc4e4 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
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| series | Stem Cells International |
| spelling | doaj-art-5a43b2c6377547aea186bd6ecf3bc4e42025-02-03T01:09:37ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/53102025310202The Effect of Vascular Endothelial Growth Factor on Bone Marrow Mesenchymal Stem Cell Engraftment in Rat Fibrotic Liver upon TransplantationKe Yuan0Chunyou Lai1Lingling Wei2Tianhang Feng3Qinyan Yang4Tianying Zhang5Tao Lan6Yutong Yao7Guangming Xiang8Xiaolun Huang9Department of Hepatobiliary-Pancreatic Surgery Center and Cell Transplantation Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Sichuan, ChinaDepartment of Hepatobiliary-Pancreatic Surgery Center and Cell Transplantation Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Sichuan, ChinaDepartment of Hepatobiliary-Pancreatic Surgery Center and Cell Transplantation Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Sichuan, ChinaDepartment of Hepatobiliary-Pancreatic Surgery Center and Cell Transplantation Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Sichuan, ChinaDepartment of Hepatobiliary-Pancreatic Surgery Center and Cell Transplantation Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Sichuan, ChinaDepartment of Hepatobiliary-Pancreatic Surgery Center and Cell Transplantation Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Sichuan, ChinaDepartment of Hepatobiliary-Pancreatic Surgery Center and Cell Transplantation Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Sichuan, ChinaDepartment of Hepatobiliary-Pancreatic Surgery Center and Cell Transplantation Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Sichuan, ChinaDepartment of Hepatobiliary-Pancreatic Surgery Center and Cell Transplantation Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Sichuan, ChinaDepartment of Hepatobiliary-Pancreatic Surgery Center and Cell Transplantation Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Sichuan, ChinaBackground. According to existing related experiments and research reports, stem cell transplantation therapy has been shown to have a positive effect on the recovery of liver fibrosis/cirrhosis, but for some reason, this therapy still cannot be widely used in clinical work. One of the reasons that cannot be ignored is the low quantity of exogenous stem cells transplanted into the liver in vivo. Thus, we investigated whether the use of the vascular endothelial growth factor (VEGF) can increase the number of stem cell transplants and improve the efficacy of stem cell transplantation therapy. Methods. Using a Sprague-Dawley rat liver fibrosis model, we transplanted into fibrosis liver allograft bone marrow mesenchymal stem cells (BMSCs) which were labelled with chlormethylbenzamido-1,1-dioctadecyl-3,3,3′3′-tetramethylin-docarbocyamine (CM-DiI) or injected VEGF adenovirus solution through the tail vein or conducted the above two operations simultaneously. The cell surface receptor profile of BMSC was examined by flow cytometry and immunofluorescence staining. Hepatic sinusoidal vascular leakage was measured with Evan’s blue dye assay. Paraffin section staining, immunofluorescent staining, RT-qPCR (quantitative reverse transcription polymerase chain reaction), and Western blot were used to evaluate hepatic pathological changes and physiology function. Result. The in vivo study indicated that, comparing with other groups of rats, the rats with combined treatment of BMSC transplantation and VEGF injection exhibited obvious reduction in liver fibrosis. Evan’s blue dye assay suggests that after injecting with VEGF adenovirus solution, the rat’s hepatic sinusoidal permeability would be increased. We confirmed the expression of very late antigen-4 (VLA4, integrin α4β1) on rat BMSCs and the elevated expression of vascular adhesion molecule-1 (VCAM-1) in the hepatic sinusoidal endothelial cells. In addition, the analysis of CM-DiI-labeled BMSCs showed that the BMSC+VEGF group exhibited better cell engraftment and that the engrafted cells were mainly distributed in the hepatic parenchyma. Furthermore, compared with the other situation, it is best to reconstitute the liver secretion and regeneration function of rats after combined application of VEGF and BMSC. Conclusion. We showed that VEGF promotes the engraftment of BMSCs in liver fibrosis, enhances liver regeneration, and improves liver function. These outcomes may be related to the increasing hepatic sinusoidal endothelium permeability and VCAM-1-increased expression.http://dx.doi.org/10.1155/2019/5310202 |
| spellingShingle | Ke Yuan Chunyou Lai Lingling Wei Tianhang Feng Qinyan Yang Tianying Zhang Tao Lan Yutong Yao Guangming Xiang Xiaolun Huang The Effect of Vascular Endothelial Growth Factor on Bone Marrow Mesenchymal Stem Cell Engraftment in Rat Fibrotic Liver upon Transplantation Stem Cells International |
| title | The Effect of Vascular Endothelial Growth Factor on Bone Marrow Mesenchymal Stem Cell Engraftment in Rat Fibrotic Liver upon Transplantation |
| title_full | The Effect of Vascular Endothelial Growth Factor on Bone Marrow Mesenchymal Stem Cell Engraftment in Rat Fibrotic Liver upon Transplantation |
| title_fullStr | The Effect of Vascular Endothelial Growth Factor on Bone Marrow Mesenchymal Stem Cell Engraftment in Rat Fibrotic Liver upon Transplantation |
| title_full_unstemmed | The Effect of Vascular Endothelial Growth Factor on Bone Marrow Mesenchymal Stem Cell Engraftment in Rat Fibrotic Liver upon Transplantation |
| title_short | The Effect of Vascular Endothelial Growth Factor on Bone Marrow Mesenchymal Stem Cell Engraftment in Rat Fibrotic Liver upon Transplantation |
| title_sort | effect of vascular endothelial growth factor on bone marrow mesenchymal stem cell engraftment in rat fibrotic liver upon transplantation |
| url | http://dx.doi.org/10.1155/2019/5310202 |
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