scholarly journals Therapeutic Effects and Repair Mechanism of HGF Gene Transfected Mesenchymal Stem Cells on Injured Endometrium via Activating Phosphorylated c-Met

2021 ◽  
Author(s):  
Xuan Xu ◽  
Jianye Wang ◽  
Liu Dong ◽  
Qiong Xing ◽  
Ying Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Akt Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Therapeutic Effects ◽  
Related Factors ◽  
Paracrine Factors ◽  
Endometrial Epithelium

Abstract BackgroundThere are many studies on the advantages of mesenchymal stem cells (MSCs) that could secret various paracrine factors in repairing endometrial injury. It is necessary to improve the stability and effectiveness of MSCs. Hepatocyte growth factor (HGF), as one of the cytokines secreted by MSCs, plays a significant role in vascular repair and mesenchymal to epithelial transformation (MET). It can be deduced that HGF is closely related to the repair process of endometrium.Therefore, we aim to investigate the effect and mechanism of MSCs from umbilical cord transfected with HGF gene in the damaged mouse endometrium.MethodsHGF gene transfected MSCs were prepared by electroporation. After determining the cell characteristics and cell activity of HGF gene transfected MSCs, the ability of HGF gene transfected MSCs to express HGF was detected by enzyme-linked immunosorbent assay. Totally, 60 female mice were randomly divided into Control group, Saline group, MSCs group , and HGF gene-transfected MSCs (MSCshgf) group. Each group of mice received treatment after injury. HE staining were used to evaluate the changes in the thickness of endometrial epithelium and the number of endometrial glands. Immunofluorescence was used to evaluate the molecular repair effect. Real time fluorescent quantitative polymerase chain reaction was used to compare the expression of angiogenesis related factors. Western blot was used to detect the activation of HGF/c-Met and AKT signaling pathways.ResultsHGF gene transfected MSCs retained the characteristics of original MSCs, and the concentration of HGF secreted by MSCs transfected with HGF gene was higher than that of normal MSCs. Compared with normal MSCs, HGF gene transfected MSCs have a more effect in promoting the repair of damaged endometrial epithelium, mainly in significantly increasing the thickness of damaged endometrial epithelium, increasing the number of glands and proliferating cells(p<0.01). Meanwhile, HGF gene transfected MSCs can improve the expression level of endometrial vascular growth related factors and promote the MET process (p<0.01). At the same time, Western blotting confirmed that these repair effects were related to HGF activation of its receptor c-Met and downstream AKT signaling pathway.ConclusionsCompared with normal MSCs, HGF gene transfected MSCs have a more significant effect in repairing the damaged endometrial epithelium. This effect is achieved by activating the receptor c-Met of HGF and downstream AKT pathway.

scholarly journals Comparison of therapeutic effects of different mesenchymal stem cells on rheumatoid arthritis in mice

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7023 ◽  
Author(s):  
Qing Zhang ◽  
Qihong Li ◽  
Jun Zhu ◽  
Hao Guo ◽  
Qiming Zhai ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Effect ◽  
Joint Destruction ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Therapeutic Effects ◽  
Micro Ct ◽  
Tnf Α

Background Rheumatoid arthritis (RA) is a chronic and nonspecific autoimmune disease, which leads to joint destruction and deformity. To investigate the potential of human mesenchymal stem cells (MSCs) as a new therapeutic strategy for patients with RA, we compared the therapeutic effects of bone marrow derived MSCs (BMSCs), umbilical cord derived MSCs (UCs), and stem cells derived from human exfoliated deciduous teeth (SHED) on collagen-induced arthritis (CIA) in mice. Methods A total of 24 DBA/1 mice were infused with type II collagen to induce RA in the experimental model. MSC-treated mice were infused with UCs, BMSCs, and SHED, respectively. Bone erosion and joint destruction were measured by micro-computed tomographic (micro-CT) analysis and hematoxylin and eosin staining. The levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were measured by immunohistochemistry and Enzyme-Linked Immunosorbent Assay (ELISA). Results Systemic delivery of MSCs significantly improved the severity of the symptoms related to CIA to greater extent compared with the untreated control group. Micro-CT revealed reduced bone erosions in the metatarsophalangeal joints upon treatment with MSCs. Additionally, according to histologic evaluation, reduced synovitis and articular destruction were observed in MSC-treated groups. The levels of TNF-α and IL-1β in the serum and joints decreased with treatment by MSCs. Conclusion Our findings suggest that systemic infusion of UCs, BMSCs, and SHED may significantly alleviate the effects of RA. The therapeutic effect of BMSCs was greater than that of SHED, while the UCs were shown to have the best therapeutic effect on CIA mice. In conclusion, compared with BMSCs and SHED, UCs may be a more suitable source of MSCs for the treatment of patients with RA.

scholarly journals Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model

2021 ◽  
Vol 40 (1) ◽  
pp. 29
Author(s):  
Nur Anna C Sa’dyah ◽  
Agung Putra ◽  
Bayu Tirta Dirja ◽  
Nurul Hidayah ◽  
Salma Yasmine Azzahara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Significant Difference ◽  
T1 And T2

Introduction<br />Liver fibrosis (LF) results from the unregulated chronic wound healing process in liver tissue. Transforming growth factor-beta (TGF-β) is the major contributing cytokine of LF promotion through activation of quiescent hepatic stellate cells (HSCs) into myofibroblasts (MFs) and increased extracellular matrix (ECM) deposition such as collagen leading to scar tissue development. Mesenchymal stem cells (MSCs) have an immunomodulatory capability that could be used as a new treatment for repairing and regenerating LF through suppression of TGF-β. This study aimed to examine the role of MSCs in liver fibrosis animal models through suppression of TGF-β levels without scar formation particularly in the proliferation phase.<br /><br />Methods<br />In this study, a completely randomized design was used with sample size of 24. Male Sprague Dawley rats were injected intraperitoneally (IP) with carbon tetrachloride (CCl4), twice weekly, for eight weeks to induce LF. Rats were randomly assigned to four groups: negative control, CCl4 group, and CCL4 + MSC-treated groups T1 and T2, at doses of 1 x 106 and 2x106 cells, respectively. TGF-β levels were analyzed by enzyme-linked immunosorbent assay (ELISA). One-way ANOVA and a least significant difference (LSD) was used to analyse the data. <br /><br />Results<br />The TGF levels of LF rat models decreased on day 7 after MSC administration. The levels of TGF-β in both MSC groups T1 and T2 decreased significantly compared with the control group (p&lt;0.05). The TGF-β suppression capability of T2 was optimal and more significant than that of T1.<br /><br />Conclusion<br />MSCs can suppress TGF levels in liver fibrosis induced rats.

scholarly journals Anti-Fibrotic Effect of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells on Skeletal Muscle Cells, Mediated by Secretion of MMP-1

2020 ◽  
Vol 21 (17) ◽  
pp. 6269
Author(s):  
Alee Choi ◽  
Sang Eon Park ◽  
Jang Bin Jeong ◽  
Suk-joo Choi ◽  
Soo-young Oh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Wharton’S Jelly ◽  
Mdx Mice ◽  
Therapeutic Effects ◽  
Paracrine Factors ◽  
Wharton's Jelly ◽  
Muscle Fibrosis ◽  
Skeletal Muscle Fibrosis

Extracellular matrix (ECM) components play an important role in maintaining skeletal muscle function, but excessive accumulation of ECM components interferes with skeletal muscle regeneration after injury, eventually inducing fibrosis. Increased oxidative stress level caused by dystrophin deficiency is a key factor in fibrosis in Duchenne muscular dystrophy (DMD) patients. Mesenchymal stem cells (MSCs) are considered a promising therapeutic agent for various diseases involving fibrosis. In particular, the paracrine factors secreted by MSCs play an important role in the therapeutic effects of MSCs. In this study, we investigated the effects of MSCs on skeletal muscle fibrosis. In 2–5-month-old mdx mice intravenously injected with 1 × 105 Wharton’s jelly (WJ)-derived MSCs (WJ-MSCs), fibrosis intensity and accumulation of calcium/necrotic fibers were significantly decreased. To elucidate the mechanism of this effect, we verified the effect of WJ-MSCs in a hydrogen peroxide-induced fibrosis myotubes model. In addition, we demonstrated that matrix metalloproteinase-1 (MMP-1), a paracrine factor, is critical for this anti-fibrotic effect of WJ-MSCs. These findings demonstrate that WJ-MSCs exert anti-fibrotic effects against skeletal muscle fibrosis, primarily via MMP-1, indicating a novel target for the treatment of muscle diseases, such as DMD.

scholarly journals Role of the Hippo signaling pathway in safflower yellow pigment treatment of paraquat-induced pulmonary fibrosis

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052090542
Author(s):  
Hai Li ◽  
Baotian Kan ◽  
Lingli Song ◽  
Yufa Liu ◽  
Xiangdong Jian
Keyword(s):  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Quantitative Polymerase Chain Reaction ◽  
Tissue Growth ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Therapeutic Effects ◽  
Hippo Signaling ◽  
Exposure Group ◽  
Tgf Β1

Objective To elucidate the molecular mechanisms by which safflower yellow (SY) mediates therapeutic effects in rats with paraquat intoxication-induced pulmonary fibrosis. Methods Rats received combinations of paraquat, SY, and SB431542, a transforming growth factor (TGF)-β1 receptor antagonist. Survival over 28 days was assessed by Kaplan–Meier analysis. Rat tissue and serum samples were assessed by hematoxylin and eosin staining, Masson’s Trichrome staining, immunoblotting, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and transmission electron microscopy. Results Survival rates were higher in SY and SB431542 groups (treatment and paraquat) than in the exposure group (paraquat alone). In the exposure group, serum TGF-β1 levels increased between days 3 and 14; mammalian STE20-like (MST) levels increased between days 3 and 7; TGF-β1 and Smad3 levels increased between days 3 and 14; and Yap and connective tissue growth factor levels increased between days 3 and 28. TGF-β1 levels were lower in SY and SB431542 groups than in the exposure group. Pathology scores were higher in exposure, SY, and SB431542 groups than in the control group throughout the experiment. Conclusions In rats with paraquat intoxication-induced pulmonary fibrosis, Hippo signaling could be activated by the MST-Yap pathway; SY and SB431542 could alleviate pulmonary fibrosis via Hippo signaling.

scholarly journals Infusion of Bone Marrow Mesenchymal Stem Cells Attenuates Experimental Severe Acute Pancreatitis in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Hang Zhao ◽  
Zhiying He ◽  
Dandan Huang ◽  
Jun Gao ◽  
Yanfang Gong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Pancreatitis ◽  
Mesenchymal Stem Cells ◽  
Survival Rate ◽  
Severe Acute Pancreatitis ◽  
Control Group ◽  
Therapeutic Effects ◽  
Isolation And Characterization ◽  
Marrow Mesenchymal Stem Cells

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.

scholarly journals Therapeutic Benefits by Human Mesenchymal Stem Cells (hMSCs) and Ang-1 Gene-Modified hMSCs after Cerebral Ischemia

2007 ◽  
Vol 28 (2) ◽  
pp. 329-340 ◽  
Author(s):  
Toshiyuki Onda ◽  
Osamu Honmou ◽  
Kuniaki Harada ◽  
Kiyohiro Houkin ◽  
Hirofumi Hamada ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cerebral Artery ◽  
Human Mesenchymal Stem Cells ◽  
Artery Occlusion ◽  
Control Group ◽  
Therapeutic Effects ◽  
Lesion Volume ◽  
Therapeutic Benefits ◽  
Cerebral Artery Occlusion

Transplantation of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has been reported to ameliorate functional deficits after cerebral artery occlusion in rats. Although several hypotheses to account for these therapeutic effects have been suggested, current thinking is that both neuroprotection and angiogenesis are primarily responsible. In this study, we compared the effects of hMSCs and angiopoietin-1 gene-modified hMSCs (Ang-hMSCs) intravenously infused into rats 6 h after permanent middle cerebral artery occlusion. Magnetic resonance imaging and histologic analyses revealed that rats receiving hMSCs or Ang-hMSCs exhibited comparable reduction in gross lesion volume as compared with the control group. Although both cell types indeed improved angiogenesis near the border of the ischemic lesions, neovascularization and regional cerebral blood flow were greater in some border areas in Ang-hMSC group. Both hMSC- and Ang-hMSC-treated rats showed greater improved functional recovery in the treadmill stress test than did control rats, but the Ang-hMSC group was greater. These results indicate the intravenous administration of genetically modified hMSCs to express angiopoietin has a similar effect on reducing lesion volume as hMSCs, but the Ang-hMSC group showed enhanced regions of increased angiogenesis at the lesion border, and modest additional improvement in functional outcome.

scholarly journals UBA2 Activates Wnt/ β-catenin Signaling Pathway during Protection of R28 Retinal Precursor Cells from Hypoxia by Extracellular Vesicles derived from Placental Mesenchymal Stem Cells

2020 ◽  
Author(s):  
Kyungmin Koh ◽  
Mira Park ◽  
Eun Soo Bae ◽  
Van-An Duong ◽  
Jong-Moon Park ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Treatment Group ◽  
Signaling Pathway ◽  
Precursor Cells ◽  
Therapeutic Effects ◽  
Label Free ◽  
Related Factors ◽  
Cell Therapies ◽  
Placental Mesenchymal Stem Cells

Abstract Background: Stem cell transplantation has been proposed as an alternative treatment for intractable optic nerve disorders characterized by irrecoverable loss of cells. Mesenchymal stem cells, with varying tissue regeneration and recovery capabilities, are being considered for potential cell therapies. To overcome the limitations of cell therapy, we isolated exosomes from human placenta–derived mesenchymal stem cells (hPMSCs), and investigated their therapeutic effects in R28 cells (retinal precursor cells) exposed to CoCl2. Method: After nine hours of exposure to CoCl2, the hypoxic damaged R28 cells were divided into non treatment group (CoCl2+R28 cells) and treatment group (CoCl2+R28 cells treated with exosome). Immunoblot analysis was performed for Pcna, Hif-1α, Vegf, Vimentin, Thy-1, Gap43, Ermn, Neuroflament, Wnt3a, β-catenin, phospo-GSK3β, Lef-1, UBA2, Skp1, βTrcp, and ubiquitin. The proteomes of each group were analyzed by liquid chromatography/tandem mass (LC-MS/MS) spectrometry. Differentially expressed proteins (DEPs) were detected by label-free quantification and the interactions of the proteins were examined through signal transduction pathway and gene ontology analysis. Result: We observed that Exosome could significantly recover proliferation damaged by CoCl2 treatment. In addition, treatment group presented the decreased expression of Hif-1α protein (P < 0.05) and increased expression of proliferation marker, Pcna, and nerve regeneration–related factors such as Vimentin, Thy-1 and Neuroflament (P < 0.05) compared with non-treatment group. In total, 200 DEPs were identified in non-treatment group and treatment group (fold change ≥ 2, p < 0.05). Catenin and ubiquitin systems (UBA2, UBE2E3, UBE2I) were found in both the DEP lists of downregulated proteins from non-treatment group and upregulated proteins from treatment group. The mRNA expressions of ubiquitin systems were significantly decreased under hypoxic condition. Moreover, UBA2 and Wnt/β-catenin protein were associated with rescue of the hypoxic damaged R28 cells. Using a siRNA system, we could find it out that hPMSC exosoms could not repair altered expressions of target proteins by CoCl2 in lacking UBA2 R28 cells. Conclusion: This study reported that hypoxic damaged expression of regeneration markers in R28 cells were significantly recovered by hPMSC exosomes. We could also demonstrate that UBA2 played a key role in activating the Wnt/β-catenin signaling pathway during protection of hypoxic damaged R28 cells, induced by hPMSC exosomes.

scholarly journals S100A8/A9 Enhances Immunomodulatory and Tissue-Repairing Properties of Human Amniotic Mesenchymal Stem Cells in Myocardial Ischemia-Reperfusion Injury

2021 ◽  
Vol 22 (20) ◽  
pp. 11175
Author(s):  
Tzu-Jou Chen ◽  
Yen-Ting Yeh ◽  
Fu-Shiang Peng ◽  
Ai-Hsien Li ◽  
Shinn-Chih Wu
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Myocardial Ischemia ◽  
Conditioned Medium ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Therapeutic Effects ◽  
Paracrine Factors ◽  
Amniotic Mesenchymal Stem Cells ◽  
Myocardial Ischemia Reperfusion

Paracrine factors of human mesenchymal stem cells (hMSCs) have the potential of preventing adverse cardiac remodeling after myocardial infarction (MI). S100A8 and S100A9 are calcium-binding proteins playing essential roles in the regulation of inflammation and fibrous tissue formation, and they might modulate the paracrine effect of hMSCs. We isolated human amniotic mesenchymal stem cells (hAMSCs) and examined the changes in the expression level of regulatory genes of inflammation and fibrosis after hAMSCs were treated with S100A8/A9. The anti-inflammatory and anti-fibrotic effects of hAMSCs pretreated with S100A8/A9 were shown to be superior to those of hAMSCs without S100A8/A9 pretreatment in the cardiomyocyte hypoxia/reoxygenation experiment. We established a murine myocardial ischemia/reperfusion model to compare the therapeutic effects of the conditioned medium of hAMSCs with or without S100A8/A9 pretreatment. We found the hearts administered with a conditioned medium of hAMSCs with S100A8/A9 pretreatment had better left ventricular systolic function on day 7, 14, and 28 after MI. These results suggest S100A8/A9 enhances the paracrine therapeutic effects of hAMSCs in aspects of anti-inflammation, anti-fibrosis, and cardiac function preservation after MI.

Directions for Enhancement of the Therapeutic Efficacy of Mesenchymal Stem Cells in Different Neurodegenerative and Cardiovascular Diseases: Current Status and Future Perspectives

2021 ◽  
Vol 16 ◽  
Author(s):  
Lamiaa A. Ahmed ◽  
Khaled F. Al-Massri
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiovascular Diseases ◽  
Neurodegenerative Disorders ◽  
Therapeutic Efficacy ◽  
Therapeutic Potential ◽  
Current Status ◽  
Therapeutic Effects ◽  
Paracrine Factors ◽  
Apoptotic Effects

: Mesenchymal stem cells (MSCs) have shown promising therapeutic effects in a wide variety of medical conditions including neurodegenerative disorders and cardiovascular diseases. Although preliminary research has emphasized the ability of MSCs to engraft at sites of injury, several studies have revealed that MSCs mediate their effects through release of various paracrine factors, and through their antioxidant, anti-inflammatory, immunomodulatory, and anti-apoptotic effects. However, the clinical implications of MSCs application are limited due to their low survival rate in conditions of inflammation, oxidative stress, and nutrient restriction in damaged areas. Furthermore, the function of isolated MSCs is usually affected by the patient’s health. Therefore, it is necessary to develop new methods to enhance the therapeutic efficacy of MSCs under pathophysiological conditions. This review provides an overview of the general properties of MSCs, their therapeutic potential in neurodegenerative disorders such as Alzheimer disease, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington disease, as well as cardiovascular diseases such as myocardial infarction, diabetic cardiomyopathy, and dilated cardiomyopathy, and their related mechanisms. In addition, this review also discusses potential problems and side effects, as well as current and future directions for improvement of MSCs therapy and their implications and applications.

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
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Radical Scavenging ◽  
Intestinal Injury ◽  
Control Group ◽  
Therapeutic Effects ◽  
Myeloperoxidase Activity ◽  
Marrow Mesenchymal Stem Cells ◽  
Nitrite Nitrate

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.

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