scholarly journals Antitumor effect of IL-12 gene-modified bone marrow mesenchymal stem cells combined with Fuzheng Yiliu decoction in an in vivo glioma nude mouse model

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jianjun Wu ◽  
Shoupin Xie ◽  
Hailong Li ◽  
Yanxia Zhang ◽  
Jia Yue ◽  
...  

Abstract Background Glioma is a complex cancer with a high morbidity and high mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown promise as an excellent cell/drug delivery vehicle for gene-targeted therapy; however, maintaining genetic stability and biological activity remains difficult. Furthermore, whether BMSCs support or inhibit tumor growth remains debated. This study investigated whether a traditional Chinese medicine fomular, Fuzheng Yiliu decoction (FYD) had a synergistic antitumor effect with IL-12 gene-modified BMSCs in glioma-bearing nude mice Methods The lentivirus-mediated IL-12 gene was transfected into primarily cultured BMSCs. A total of 72 BALB/c nude mice were used to establish xenograft models with glioma U251 cells and were divided into groups (n = 12) including blank control group, nude mouse model group (model group), lentiviral transfection of BMSC group with no gene loading (BMSC group), IL-12 lentivirus-transfected BMSC group (IL-12 + BMSC group), FYD treatment group (FYD group), and FYD treatment in IL-12 lentivirus-transfected BMSC group (FYD + IL-12 + BMSC group).. After treatment for 14 days, all mice were sacrificed to collect tumor tissue and serum for more detection, such as distribution of BMSCs, cell apoptosis in xenograft tumors, serum IL-12 and INF-γ levels, mouse weight and tumor volume were measured Results There were significantly more apoptotic cells in tumor tissue in IL-12 gene transfected group, FYD treatment group and FYD combining with IL-12 gene transfected group than that in the model group (P < 0.05). The FYD + IL-12 + BMSC group showed significantly higher Bax and lower Bcl-2 expression (P < 0.05), and serum IL-12 and INF-γ levels (P < 0.05) were higher than that in all other groups. After the intervention, this group also showed a strong inhibitory effect against tumor growth (P < 0.05) Conclusions This study suggested FYD treatment combined with IL-12 gene-modified BMSCs shows synergistic antitumor effect in glioma-bearing nude mice.

2020 ◽  
Author(s):  
Jianjun Wu ◽  
Shoupin Xie ◽  
Hailong Li ◽  
Yanxia Zhang ◽  
Jia Yue ◽  
...  

Abstract Background: Glioma is a complex cancer with a high morbidity and high mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown promise as an excellent cell/drug delivery vehicle for gene-targeted therapy; however, maintaining genetic stability and biological activity remains difficult. Furthermore, whether BMSCs support or inhibit tumor growth remains debated. This study investigated whether a traditional chinese medicine fomular, Fuzheng Yiliu decoction (FYD) had a synergistic antitumor effect with IL-12 gene-modified BMSCs in glioma-bearing nude mice.Methods: The lentivirus-mediated IL-12 gene was transfected into primarily cultured BMSCs. A total of 72 BALB/c nude mice were used to establish xenograft models with glioma U251 cells and were divided into 6 groups (n = 12) including negative control group, nude mouse model group, lentiviral empty vector transfection into BMSC group, IL-12 gene lentivirus transfection into BMSC group and FYD treatment of IL-12 lentivirus-transfected BMSC group. After treatment for 14 days, all mice were sacrificed to collect tumor tissue and serum for more detection, such as distribution of BMSCs, cell apoptosis in xenograft tumors, serum IL-12 and INF-γ levels, mouse weight and tumor volume were measured.Results: There were significantly more apoptotic cells in tumor tissue in IL-12 gene transfected group, FYD treatment group and FYD combining with IL-12 gene transfected group than that in the model group (P < 0.05). The FYD+IL-12+BMSC group showed significantly higher Bax and lower Bcl-2 expression (P < 0.05), and serum IL-12 and INF-γ levels (P < 0.05) were higher than that in all other groups. After the intervention, this group also showed a strong inhibitory effect against tumor growth (P < 0.05).Conclusions: This study suggested FYD treatment combined with IL-12 gene-modified BMSCs shows synergistic antitumor effect in glioma-bearing nude mice.


2022 ◽  
Vol 12 (3) ◽  
pp. 634-640
Author(s):  
Changtao Fu ◽  
Youdong Zhou ◽  
Lei Wang

Bone marrow mesenchymal stem cells (BMSCs) can be differentiated into a variety of cells and repair damaged cells. We explore whether BMSCs can repair brain damage and synapses regeneration in mice under intrauterine ischemia and hypoxia. Twenty-five pregnant mice were assigned into control group, 6% hypoxic injury group, 8% hypoxic injury group, 6% treatment group, 8% treatment group followed by analysis of the expression of MBP, MAG, CSPGs, IGF-1, NCAN, COLIV, SynD1G1, GFAP, GSK-3β, and β-actin by RT-PCR and Western blot. Our results showed that the expression of MBP, MAG, COL IV, SynD1G1, IGF-1 in the treatment group were significantly higher than those in hypoxic injury group with significant differences between the 8% treatment group and 6% treatment group (P < 0.05). In conclusion, BMSCs can repair brain damage and synapse regeneration in mice under different intrauterine ischemia and hypoxia conditions which might be through Wnt signaling pathway.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Shutian Shi ◽  
Xingxin Wu ◽  
Xiao Wang ◽  
Wen Hao ◽  
Huangtai Miao ◽  
...  

Bone marrow mesenchymal stem cells (BMMSCs) are used in cardiac tissue engineering for the regeneration of diseased hearts. We examined the differentiation of rat BMMSCs into cardiomyocyte-like cells when induced with a combined low dose treatment of transforming growth factor-β1 (TGF-β1) and 5-azacytidine (5-AZA). Results showed that cell proliferation in the combined low dose treatment group of TGF-β1 and 5-AZA was increased compared with the TGF-β1 group or the 5-AZA group. The cell apoptosis was relieved by combined TGF-β1 and 5-AZA treatment compared to 5-AZA treatment alone. The number of cells positive for myosin heavy chain, connexin-43,α-actin, and troponin I in the combined treatment group was higher than those observed in the TGF-β1 group or the 5-AZA group. Moreover, the combined low dose treatment group of TGF-β1 and 5-AZA reveals the strongest expression of troponin I,α-actin, and phosphorylated extracellular signal-regulated protein kinases 1 and 2 (p-ErK1/2) among the treatment groups. These results suggest that the combined low dose treatment of TGF-β1 and 5-AZA can improve the differentiation potential of rat BMMSCs into cardiomyocyte-like cells and alleviate cell damage effectsin vitro. The mechanism that is involved in influencing differentiation may be associated with p-ErK1/2.


2021 ◽  
Author(s):  
Yuan Liwei ◽  
Cao Jia ◽  
Hu Mingyue ◽  
Xu Dabao ◽  
Li Yan ◽  
...  

Abstract Background: Although the effect of bone marrow mesenchymal stem cells (BMSCs) combined with estrogen therapy in the repair of endometrial injury has been confirmed, its underlying molecular mechanism in intrauterine adhesion (IUA) remains unclear. In this study, we aim to investigate the effect and involvement of a combination of BMSCs with estrogen in restoration of injured endometrium by applying a rabbit endometrial injury model. Method: BMSCs were isolated and labeled with PKH26 fluorescent dye. The IUA animal model was generated by a dual damage method of mechanical curettage and lipopolysaccharide infection. Rabbits were randomly assigned to the following 5 groups: sham operation group, IUA model group, E2 treatment group, BMSCs treatment group, and BMSCs combined with E2 treatment group. Bilateral uterus were obtained at different time points for the further study. HE and Masson staining were used to evaluate the number of endometrial glands and the degree of fibrosis. The expression of fibrosis and EMT related markers were observed by Immunohistochemical, immunofluorescence staining and Western blot. The expression of core molecules in the Wnt/β-catenin signaling pathway was examined by Western blot.Results: In the present study, it is found that PKH26 fluorescent dye can successfully label BMSCs and track the distribution and differentiation of transplanted BMSCs. BMSCs differentiated into endometrial epithelial cells and mainly located around the endometrial glands and extracellular matrix at 3 or 5 days post-transplantation, while BMSCs primarily differentiated into endometrial stromal cells at 7 days after orthotopic transplantation. Furthermore, after combined treatment of BMSCs and estrogen, the number of glands increased significantly, and the area of fibrosis reduced evidently, accompanied by a downregulation of mesenchymal markers and upregulation of epithelial markers when compared with each single treatment group. The expression levels of core molecules in the Wnt/β-catenin signaling pathway were higher in the BMSCs+E2 group than in the other treatment groups. Conclusions: Our study demonstrates that BMSCs combined with estrogen can improve the repair after endometrial injury by promoting the proliferation of endometrial epithelial cells and inhibiting EMT and endometrial fibrosis. This combined effect is achieved in part through activation of the Wnt/β-catenin signaling pathway.


2013 ◽  
Vol 22 (1) ◽  
pp. 133-145 ◽  
Author(s):  
Mahmoud M. Gabr ◽  
Mahmoud M. Zakaria ◽  
Ayman F. Refaie ◽  
Amani M. Ismail ◽  
Mona A. Abou-El-Mahasen ◽  
...  

2013 ◽  
Author(s):  
Melo Ocarino Natalia de ◽  
Silvia Silva Santos ◽  
Lorena Rocha ◽  
Juneo Freitas ◽  
Reis Amanda Maria Sena ◽  
...  

2014 ◽  
Author(s):  
Reis Amanda Maria Sena ◽  
Freitas Silva Juneo de ◽  
Silvia Silva Santos ◽  
Rogeria Serakides ◽  
Melo Ocarino Natalia de

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