scholarly journals Effect of Bone Marrow and Adipose Mesenchymal Stem Cells on Rat Intestinal Injury Induced by Methotrexate

2018 ◽  
Vol 1 (2) ◽  
pp. 1-11
Author(s):  
Marwa A. Masoud ◽  
Eman G. Mohamed ◽  
Wedad A. Hassan ◽  
Ebtehal Mohammad F

Methotrexate (MTX) is an anti-metabolite in cancer chemotherapy and is associated with various toxicities assigned to inflammation and oxidative stress. The present study was undertaken to corroborate the therapeutic effects of bone marrow mesenchymal stem cells (BM-MSCs) and adipose-derived mesenchymal stem cells (AD-MSCs) in MTX-induced intestinal toxicity in experimental animals as compared with dexamethasone (Dex). Rats were divided into five groups: I-Normal control group, II- MTX (14 mg/kg, as a single dose/week for 2 weeks), III & IV- BM-MSCs & AD-MSCs (2 × 106 cells/rat, 1 week after last dose of MTX), respectively, plus V- Dex (0.5 mg/kg/ for 7 days, 1 week after last dose of MTX). MTX induced marked intestinal elevation of interleukin-6, total oxidant, and nitrite/ nitrate, caspase-3 contents and myeloperoxidase activity, along with the reduction of reduced glutathione content and catalase activity. In conclusion, the positive modulation of MTX toxicity could be attributed to the free radical scavenging, anti-inflammatory and antiapoptotic potential of BM-MSC and AD-MSCs which will possibly make them as remarkable hopeful for the treatment of intestinal injury.

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Hang Zhao ◽  
Zhiying He ◽  
Dandan Huang ◽  
Jun Gao ◽  
Yanfang Gong ◽  
...  

Background & Aims. Severe acute pancreatitis (SAP) remains a high-mortality disease. Bone marrow (BM) mesenchymal stem cells (MSCs) have been demonstrated to have plasticity of transdifferentiation and to have immunomodulatory functions. In the present study, we assessed the roles of MSCs in SAP and the therapeutic effects of MSC on SAP after transplantation.Methods. A pancreatitis rat model was induced by the injection of taurocholic acid (TCA) into the pancreatic duct. After isolation and characterization of MSC from BM, MSC transplantation was conducted 24 hrs after SAP induction by tail vein injection. The survival rate was observed and MSCs were traced after transplantation. The expression of TNF-αand IL-1βmRNA in the transplantation group was also analyzed.Results. The survival rate of the transplantation group was significantly higher compared to the control group (p<0.05). Infused MSCs were detected in the pancreas and BM 3 days after transplantation. The expression of TNF-αand IL-1βmRNA in the transplantation group was significantly lower than in the control group in both the pancreas and the lungs (p<0.05).Conclusions. MSC transplantation could improve the prognosis of SAP rats. Engrafted MSCs have the capacity of homing, migration, and planting during the treatment of SAP.


2021 ◽  
Vol 25 (19) ◽  
pp. 9281-9294
Author(s):  
Yi Jin ◽  
Min Xu ◽  
Hai Zhu ◽  
Chen Dong ◽  
Juan Ji ◽  
...  

2022 ◽  
Vol 12 (5) ◽  
pp. 1034-1039
Author(s):  
Xiaoxiang Wang ◽  
Lan Yu ◽  
Xing Xiong ◽  
Yao Chen ◽  
Bo Men

Bone marrow mesenchymal stem cells (BMSCs) are capable of multipolar differentiation and repairing injured tissues. Herein, we aimed to investigate the mechanism by how BMSCs modulate the apoptotic pathway in the acute pancreatitis (AP). In this study, primary BMSCs were cultured and administrated into 10 AP mice while 10 healthy mice were taken as a blank group and 10 AP mice as a control group. The mouse pancreatic tissues were assessed by HE staining and evaluated by pancreatitis score and serum amylase detection. Level of inflammatory factors CRP and TNF-α was measured by ELISA and PIPK1, PIPK3, MLKL and Caspase-8 expression was detected by RT-qPCR and Western blot. The pancreatitis score (7.29±1.36) and the serum amylase score of (453.66±103.67) mu/ml of BMSCs group was significantly higher than that of control group, indicating increased tissue repair after BMSCs treatment. BMSCs group exhibited a higher level of CRP (711.01±115.31) and TNF-α (132.81±22.13) in serum compared to control group (p < 0.05). PIPK1, PIPK3, and MLKL expression in BMSCs group decreased (p < 0.05) whereas Caspase-8 was increased (p < 0.05). On the other hand, BMSCs group presented upregulated PIPK1, PIPK3, and MLKL (p < 0.05) and downregulated Caspase-8 (p < 0.05). In conclusion, BMSCs regulate cell apoptosis by upregulating Caspase-8 expression, and downregulating PIPK1, PIPK3 and MLKL level, thereby alleviating the inflammation in AP.


2020 ◽  
Vol 10 (12) ◽  
pp. 1865-1870
Author(s):  
Yang Ying ◽  
Binghao Zhao ◽  
Wei Qian ◽  
Li Xu

Bone marrow mesenchymal stem cells (BMSCs) have self-renewal potential with multi-directional differentiation. Progranulin prevents bone degradation, inhibits inflammation and protects bone tissue. However, the role of Progranulin in osteoporotic BMSCs is unclear. Osteoporosis (OP) rat models were prepared by ovarian removal and treated with different doses (5 and 10 μM) of Progranulin followed by analysis of BMP-2 level by ELISA, bone mineral density and ALP activity. OP rat BMSCs were isolated and assigned into control group and Progranulin group followed by analysis of Progranulin level by ELISA, cell proliferation by MTT assay, RUNX2 and COL1A1 mRNA level by Real time PCR, and PI3K/Akt/PPARγ signaling protein level by Western blot. Progranulin treatment of OP rats dose-dependently increased BMP-2 expression, bone density and ALP activity. Compared with OP group, there were significant differences (P <0.05). Progranulin expression and BMSCs proliferation was increased, and RUNX2 and COL1A1 mRNA expression was elevated in Progranulin-treated OP group along with increased PI3K/Akt expression and decreased PPARγ protein expression. Compared with OP group, the difference was statistically significant, and the change was more significant with increasing concentration (P <0.05). Progranulin promotes BMSCs osteogenic differentiation and proliferation by regulating PI3K/Akt/PPARγ signaling pathway, which is beneficial for OP rats’ bone synthesis.


2021 ◽  
Vol 11 (7) ◽  
pp. 1327-1332
Author(s):  
Long Zhou ◽  
Kui Wang ◽  
Meixia Liu ◽  
Wen Wei ◽  
Liu Liu ◽  
...  

NF-κB activation and its abnormal expression are involved in the progression of glioma. miRNA plays a crucial role in bone diseases. The role of NF-κB is becoming more and more important. The purpose of this study is to explore the mechanism by how miR-1 regulates NF-κB signaling. C57 glioma mouse models were divided into osteoporosis (OP) group and control group. qPCR was used to measure miR-1 levels in OP and control mice. Bone marrow mesenchymal stem cells (BMSCs) were cultured and transfected with miR-1 specific siRNA to establish miR-1 knockout cell model followed by analysis of cell apoptosis, expression of NF-κB signaling molecules by western blot. qPCR results showed that miR-1 levels in OP mice were significantly reduced compared to control mice. A large number of siRNA particles were observed in transfected BMSCs under a fluorescence microscope. qPCR results showed that siRNA transfection significantly suppressed miR-1, indicating successful transfection. Flow cytometry revealed significant differences in cell apoptosis between miR-1 siRNA group and the NC group. Western blot indicated miR-1 promoted BMSCs differentiation via NF-κB mediated up-regulation of ALP activity. The expression of miR-1 is low in BMSCs of mice with glioma. In addition, BMSCs differentiation is enhanced by NF-κB activation via up-regulating miR-1.


2020 ◽  
pp. 229255032096740
Author(s):  
Qin Yonghong ◽  
Li Aishu ◽  
Yazan Al-Ajam ◽  
Liao Yuting ◽  
Zhang Xuanfeng ◽  
...  

Current wound healing models generally employ full-thickness or irregular split wounds. Consequently, assessing the type of healing at varying wound depths and determining the deepest level at which wounds can regenerate has been a challenge. We describe a wound model that allows assessment of the healing process over a continuous gradient of wound depth, from epidermal to full-thickness dermal loss. Further, we investigate whether green fluorescent protein–labeled bone marrow mesenchymal stem cells (BM-MSCs/GFP) transplantation could regenerate deeper wounds that might otherwise lead to scar formation. A wound gradient was created on the back of 120 Sprague Dawley rats, which were randomized into the BM-MSCs/GFP and control group. These were further subdivided into 6 groups where terminal biopsies of the healing wounds were taken at days 1, 3, 5, 7, 14, and 21 post-operatively. At each observed time point, the experimental animals were anesthetized and photographed, and depending on the group, the animals euthanized and skin taken for rapid freezing, haemotoxylin and eosin staining, and vascular endothelial growth factor (VEGF) immunohistochemistry. We found the deepest layer to regenerate in the control group was at the level of the infundibulum apex, while in the BM-MSCs/GFP group this was deeper, at the opening site of sebaceous duct at hair follicle in which had the appearance of normal skin and less wound contraction than the control group ( P value less than .05). The expression of VEGF in BM-MSCs/GFP group was higher than that in control group ( P value less than .05). The number of vessels increased from 2.5 ± 0.2/phf of control group to 5.0 ± 0.3/phf of BM-MSCs/GFP ( P value less than .05). The progressively deepening wound model we described can identify the type of wound repair at increasing depths. Further, topical transplantation of BM-MSCs/GFP significantly improved regeneration of deeper wounds from infundibulum apex (maximum depth of control group regeneration) to the opening site of sebaceous duct at hair follicle level.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5133-5133
Author(s):  
Jun Ren ◽  
Hanfang Jiang ◽  
Lijun Di ◽  
Guohong Song

Abstract Background and Aim: Bone marrow stem cells can differentiate into mature hepatocytes in vitro and in vivo. Moreover, recent study shown bone marrow mesenchymal stem cells (MSCs) are the most potent component in hepatic differentiation, suggesting that the transplantation of MSCs is a promising treatment for liver disease. However, little information is available about the therapeutic potential of MSCs transplantation in cases of hepatic cell carcinoma (HCC). Here, we transplanted bone marrow-derived MSCs to testify their effects in a murine model of orthotopic HCC. Methods:MSCs were obtained from tow male strains of β-galactosidase (β-gal) transgenic mouse(Rosa 26) and BALB/c mouse. MSCs were injected into tumor in BALB/c femal murine models of orthotopic HCC. Tumor growths were assessed by MRI on 7 days and survival rates were observed. When mouse was dying, the liver was removed from each treated mouse and evaluated by x-gal staining, and immunohistochemisty as well. Results: MSCs transplantation increased the survival of hepatocellular carcinoma-bearing mice(25.5±4.5days verus 21.3±1.7days, p=0.025) and decreased tumor diameter slightly (7.7±2.9mm versus 9.4±2.8mm, p=0.284). MSCs transplanted directly into the tumor and/ or normal hepatic parenchyma in the same liver lobe localized mainly at the border between the tumor cells and normal liver parenchyma, induced a large area of coagulative necrosis in the tumor bed. Some engrafted MSCs were positive for albumin. There are in the carcinoma bearing BALB/c mice with MSCs implanted, whether MSCs from BALB/c mice or from Rosa 26 transgenic mice. Conclusion: Our results suggest that the therapeutical effects of MSCs might be mediated not only by their differentiation into hepatocyte, but also mainly by they possess intrinsic antineoplastic properties.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chuan Tian ◽  
Jie He ◽  
Yuanyuan An ◽  
Zailing Yang ◽  
Donghai Yan ◽  
...  

Abstract Background Female sex hormone secretion and reproductive ability decrease with ageing. Bone marrow mesenchymal stem cells (BMMSCs) have been postulated to play a key role in treating ovarian ageing. Methods We used macaque ovarian ageing models to observe the structural and functional changes after juvenile BMMSC treatment. Moreover, RNA-seq was used to analyse the ovarian transcriptional expression profile and key pathways through which BMMSCs reverse ovarian ageing. Results In the elderly macaque models, the ovaries were atrophied, the regulation ability of sex hormones was reduced, the ovarian structure was destroyed, and only local atretic follicles were observed, in contrast with young rhesus monkeys. Intravenous infusion of BMMSCs in elderly macaques increased ovarian volume, strengthened the regulation ability of sex hormones, reduced the degree of pulmonary fibrosis, inhibited apoptosis, increased density of blood vessels, and promoted follicular regeneration. In addition, the ovarian expression characteristics of ageing-related genes of the elderly treatment group reverted to that of the young control group, 1258 genes that were differentially expressed, among which 415 genes upregulated with age were downregulated, 843 genes downregulated with age were upregulated after BMMSC treatment, and the top 20 differentially expressed genes (DEGs) in the protein-protein interaction (PPI) network were significantly enriched in oocyte meiosis and progesterone-mediated oocyte maturation pathways. Conclusion The BMMSCs derived from juvenile macaques can reverse ovarian ageing in elderly macaques.


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