Chinese Journal of Tissue Engineering Research ›› 2021, Vol. 25 ›› Issue (25): 3988-3993.doi: 10.12307/2021.009

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Bone marrow mesenchymal stem cells overexpressing prolyl oligopeptidase on the repair of liver fibrosis in rat models

Hao Xiaona, Zhang Yingjie, Li Yuyun, Xu Tao   

  1. School of Laboratory Medicine, Bengbu Medical College, Bengbu 233030, Anhui Province, China
  • Received:2020-09-17 Revised:2020-09-19 Accepted:2020-10-29 Online:2021-09-08 Published:2021-03-25
  • Contact: Zhang Yingjie, Master, Associate professor, School of Laboratory Medicine, Bengbu Medical College, Bengbu 233030, Anhui Province, China
  • About author:Hao Xiaona, Master, Lecturer, School of Laboratory Medicine, Bengbu Medical College, Bengbu 233030, Anhui Province, China
  • Supported by:
    the Science and Technology Development Fund of Bengbu Medical College, No. BYKF1729 (to ZYJ); the Key Scientific Research Project of Colleges and Universities of Anhui Provincial Department of Education, No. KJ2019A0391 (to ZYJ)

Abstract: BACKGROUND: How to make the transplanted mesenchymal stem cells survive and function better is one of the hot spots in the research of mesenchymal stem cells.
OBJECTIVE: To investigate the repair function of bone marrow mesenchymal stem cells overexpressing prolyl oligopeptidase on liver fibrosis in rats and explore the related mechanisms.
METHODS:  Five rats were randomly selected from 35 male Sprague-Dawley rats into the normal control group (n=5). The remaining 30 rats were injected subcutaneously with CCl4 peanut oil solution to prepare rat liver fibrosis models. After successful modeling, they were randomly divided into model injury group (n=10), bone marrow mesenchymal stem cells group (n=10), and prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells group (n=10). The model injury group was given normal saline via the tail vein. Bone marrow mesenchymal stem cells group was given 1×106 bone marrow mesenchymal stem cells. The prolyl oligopeptidase overexpression bone marrow mesenchymal stem cells group was given 1×106 prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells. Three weeks later, the rats were sacrificed. The inferior vena cava blood of each group was collected to detect liver function and liver fibrosis indicators. The liver was taken out and stained with hematoxylin-eosin to observe the pathological changes. Cell localization was observed under a fluorescence microscope. Western blot assay was conducted to detect the expression level of transforming growth factor-β protein in the liver.  
RESULTS AND CONCLUSION: (1) The liver function and fibrosis indexes of rats in the bone marrow mesenchymal stem cells group and prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells group were significantly improved compared with the model injury group, and the improvement was more obvious in the prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells group (P < 0.05). (2) Fluorescence microscope of frozen section of rat liver tissue showed that there were green fluorescent cells in the prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells group, indicating that bone marrow mesenchymal stem cells were successfully colonized in the rat liver. (3) Hematoxylin-eosin staining of liver tissue indicated that the degree of liver fibrosis in the bone marrow mesenchymal stem cells and prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells groups was significantly improved, and the liver pathology of the prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells group was closer to normal. (4) The expression level of transforming growth factor-β protein in the bone marrow mesenchymal stem cells group and prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells group was significantly lower than that of the model injury group (P < 0.05), and the decrease in the prolyl oligopeptidase-overexpressed bone marrow mesenchymal stem cells group was more obvious (P < 0.05). (5) Results verify that overexpression of prolyl oligopeptidase can significantly improve the repair ability of bone marrow mesenchymal stem cells on liver fibrosis.

Key words: stem cells, bone marrow mesenchymal stem cells, prolyl oligopeptidase, overexpression, liver fibrosis, transforming growth factor-β, rats

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