scholarly journals Dysregulation of Angiogenesis and Inflammatory Genes in Endometrial Mesenchymal Stem Cells and Their Contribution to Endometriosis

Author(s):  
Shermineh Heydari ◽  
Ladan Kashani ◽  
Mehrdad Noruzinia

Endometriosis is a common, chronic, inflammatory disorder in women, characterized by the presence of endometrial tissue outside the uterus cavity. The disease affects ~10% of women during their reproductive age. There are some debates on the pathogenesis of endometriosis and its mechanism among scientists; therefore, different hypotheses have been suggested. According to Sampson's theory, a possible mechanism for seeding ectopic endometriotic lesions is a dysregulation of endometrial mesenchymal stem cells (eMSCs). In the present study, we evaluated the expression of candidate genes in eMSCs obtained from endometriosis patients and compared them with non-endometriosis female patients. In addition, bioinformatic analysis was conducted to uncover the genes in the list of our co-expression gene network in endometriosis. According to our results, the expression of vascular endothelial growth factor A, C-X-C-motif chemokine ligand 8, interleukin-6, and intercellular adhesion molecule-1 genes were up-regulated in the eMSCs isolated from endometriosis patients. There was no significant difference in the expression of the LaminB1 gene between the endometriosis and non-endometriosis patients. On the other hand, our bioinformatics analysis demonstrated that co-expressed genes were enriched in the cytokine signaling pathway. Our study provides valuable insights into the gene expression dysregulation in eMSCs derived from endometriosis patients and suggests a possible function for co-expressed networks in the pathogenesis of endometriosis. To confirm the results, more investigations are required.

2007 ◽  
Vol 361-363 ◽  
pp. 1173-1176
Author(s):  
Jun Wang ◽  
Yu Bo Fan ◽  
Zhi He Zhao ◽  
Juan Li ◽  
Jun Liu

Osteoblasts were perceived as pivotal cells, recognized as the cells that control both the formative and the resorptive phases of the bone remodeling cycle. Osteoblasts were an essential requirement for osteoclastogenesis though expressing or secreating bioactive osteoclast-differentiation-regulatory proteins, osteoclast differentiation factor (ODF)was the most important factor among these, ODF participate nearly in every step of differentiation and activation of osteoclasts. In addition, intercellular adhesion molecule-1 (ICAM-1)and its receptors LFA-1 play a role in osteoclast development by affecting adhesion between stromal cells and osteoclast progenitors before the occurrence of ODF-ODF receptor signaling. However, it is not clear about the relationship between ODF, ICAM-1 expression of osteoblasts and differentiation state of osteoblasts. So,the aim of this study was to investgate whether the expression of ODF, ICAM-1 depended on the stage of osteoblastic differentiation from rat bone marrow mesenchymal stem cells(rBMSCs). The viability of rBMSCs is reduced significantly by osteogenic inducement as differentiating into osteoblasts, ALPase activity of OS-treated rBMSCs was enhanced obviously within 9 days , declined subsequently and recovered nearly the original level at day 14. Expression of ODF is enhanced with osteogenic differentiation guadully. whereas, expression of ICAM-1 is activated at OS-treated day 6, then keeping at a stable level. This study indicated that rBMSCs undergoing osteogenic inducement was an ideal model for studying the differentiation and maturation of osteoblasts. During the early stage of differentiation along osteoblasts from stem cells to osteocytes, rBMSCs or Osteoprogenitor react somewhat differently from osteoblasts, suggesting the ability of osteoblasts to regulating differentiation and maturation of osteoclasts have been improved with osteogenic culture.


Author(s):  
Hariharan Jayaraman ◽  
Nalinkanth V. Ghone ◽  
Ranjith Kumaran R ◽  
Himanshu Dashora

: Mesenchymal stem cells because of its high proliferation, differentiation, regenerative capacity, and ease of availability have been a popular choice in cytotherapy. Mesenchymal Stem Cells (MSCs) have a natural tendency to home in a tumor microenvironment and acts against it, owing to the similarity of the latter to an injured tissue environment. Several studies have confirmed the recruitment of MSCs by tumor through various cytokine signaling that brings about phenotypic changes to cancer cells, thereby promoting migration, invasion, and adhesion of cancer cells. The contrasting results on MSCs as a tool for cancer cytotherapy may be due to the complex cell to cell interaction in the tumor microenvironment, which involves various cell types such as cancer cells, immune cells, endothelial cells, and cancer stem cells. Cell to cell communication can be simple or complex and it is transmitted through various cytokines among multiple cell phenotypes, mechano-elasticity of the extra-cellular matrix surrounding the cancer cells, and hypoxic environments. In this article, the role of the extra-cellular matrix proteins and soluble mediators that acts as communicators between mesenchymal stem cells and cancer cells has been reviewed specifically for breast cancer, as it is the leading member of cancer malignancies. The comprehensive information may be beneficial in finding a new combinatorial cytotherapeutic strategy using MSCs by exploiting the cross-talk between mesenchymal stem cells and cancer cells for treating breast cancer.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247662
Author(s):  
Jingjing He ◽  
Desheng Kong ◽  
Zhifen Yang ◽  
Ruiyun Guo ◽  
Asiamah Ernest Amponsah ◽  
...  

Background Diabetes mellitus as a chronic metabolic disease is threatening human health seriously. Although numerous clinical trials have been registered for the treatment of diabetes with stem cells, no articles have been published to summarize the efficacy and safety of mesenchymal stem cells (MSCs) in randomized controlled trials (RCTs). Methods and findings The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to provide a reliable numerical summary and the most comprehensive assessment of therapeutic efficacy and safety with MSCs in diabetes. PubMed, Web of Science, Ovid, the Cochrane Library and CNKI were searched. The retrieval time was from establishment of these databases to January 4, 2020. Seven RCTs were eligible for analysis, including 413 participants. Meta-analysis results showed that there were no significant differences in the reduction of fasting plasma glucose (FPG) compared to the baseline [mean difference (MD) = -1.05, 95% confidence interval (CI) (-2.26,0.16), P<0.01, I2 = 94%] and the control group [MD = -0.62, 95%CI (-1.46,0.23), P<0.01, I2 = 87%]. The MSCs treatment group showed a significant decrease in hemoglobin (Hb) A1c [random-effects, MD = -1.32, 95%CI (-2.06, -0.57), P<0.01, I2 = 90%] after treatment. Additionally, HbA1c reduced more significantly in MSC treatment group than in control group [random-effects, MD = -0.87, 95%CI (-1.53, -0.22), P<0.01, I2 = 82%] at the end of follow-up. However, as for fasting C-peptide levels, the estimated pooled MD showed that there was no significant increase [MD = -0.07, 95%CI (-0.30, 0.16), P<0.01, I2 = 94%] in MSCs treatment group compared with that in control group. Notably, there was no significant difference in the incidence of adverse events between MSCs treatment group and control group [relative risk (RR) = 0.98, 95%CI (0.72, 1.32), P = 0.02, I2 = 70%]. The most commonly observed adverse reaction in the MSC treatment group was hypoglycemia (29.95%). Conclusions This meta-analysis revealed MSCs therapy may be an effective and safe intervention in subjects with diabetes. However, due to the limited studies, a number of high-quality as well as large-scale RCTs should be performed to confirm these conclusions.


Author(s):  
Nur Anna C Sa’dyah ◽  
Agung Putra ◽  
Bayu Tirta Dirja ◽  
Nurul Hidayah ◽  
Salma Yasmine Azzahara ◽  
...  

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.


Author(s):  
Desi Sandra Sari ◽  
Fourier Dzar Eljabbar Latief ◽  
Ferdiansyah ◽  
Ketut Sudiana ◽  
Fedik Abdul Rantam

The tissue engineering approach for periodontal tissue regeneration using a combination of stem cells and scaffold has been vastly developed. Mesenchymal Stem Cells (MSCs) seeded with Bovine Teeth Scaffold (BTSc) can repair alveolar bone damage in periodontitis cases. The alveolar bone regeneration process was analyzed by micro-computed tomography (µ-CT) to observe the structure of bone growth and to visualize the scaffold in 3-Dimensional (3D). The purpose of this study is to analyze alveolar bone regeneration by µ-CT following the combination of MSCs and bovine teeth scaffold (MSCs-BTSc) implantation in the Wistar rat periodontitis model. Methods. MSCs were cultured from adipose-derived mesenchymal stem cells of rats. BTSc was taken from bovine teeth and freeze-dried with a particle size of 150-355 µm. MSCs were seeded on BTSc for 24 hours and transplanted in a rat model of periodontitis. Thirty-five Wistar rats were made as periodontitis models with LPS induction from P. gingivalis injected to the buccal section of interproximal gingiva between the first and the second mandibular right-molar teeth for six weeks. There were seven groups (control group, BTSc group on day 7, BTSc group on day 14, BTSc group on day 28, MSCs-BTSc group on day 7, MSCs-BTSc group on day 14, MSCs-BTSc group on day 28). The mandibular alveolar bone was analyzed and visualized in 3D with µ-CT to observe any new bone growth. Statistical Analysis. Group data were subjected to the Kruskal Wallis test followed by the Mann-Whitney (p <0.05). The µ-CT qualitative analysis shows a fibrous structure, which indicates the existence of new bone regeneration. Quantitative analysis of the periodontitis model showed a significant difference between the control model and the model with the alveolar bone resorption (p <0.05). The bone volume and density measurements revealed that the MSCs-BTSc group on day 28 formed new bone compared to other groups (p <0.05). Administration of MSCs-BTSc combination has the potential to form new alveolar bone.


Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000011440
Author(s):  
Jong-Won Chung ◽  
Won Hyuk Chang ◽  
Oh Young Bang ◽  
Gyeong Joon Moon ◽  
Suk Jae Kim ◽  
...  

ObjectiveTo test whether autologous modified mesenchymal stem cells (MSCs) improve recovery in patients with chronic major stroke.MethodsIn this prospective, open-label, randomized controlled trial with blinded outcome evaluation, patients with severe middle cerebral artery territory infarct within 90 days of symptom onset were assigned, in a 2:1 ratio, to receive preconditioned autologous MSC injections (MSC group) or standard treatment alone (control group). The primary outcome was the score on the modified Rankin Scale (mRS) at 3 months. The secondary outcome was to further demonstrate motor recovery.ResultsA total of 39 and 15 patients were included in the MSC and control groups, respectively, for the final intention-to-treat analysis. Mean age of patients was 68 (range, 28–83) years, and mean interval between stroke onset to randomization was 20.2 (range, 5–89) days. Baseline characteristics were not different between groups. There was no significant difference between the groups in the mRS score shift at 3 months (p = 0.732). However, secondary analyses showed significant improvements in lower extremity motor function in the MSC group compared to the control group (change in the leg score of the Motricity Index, p = 0.023), which was notable among patients with low predicted recovery potential. There were no serious, treatment-related adverse events.ConclusionsIntravenous application of preconditioned, autologous MSCs with autologous serum was feasible and safe in patients with chronic major stroke. MSC treatment was not associated with improvements in the 3-month mRS score, but we did observe leg motor improvement in detailed functional analyses.Classification of evidenceThis study provides Class III evidence that autologous mesenchymal stem cells do not improve 90-day outcomes in patients with chronic stroke.Trial registrationclinicaltrials.gov Identifier: NCT01716481.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Zhang Chen ◽  
Yang Yun ◽  
Nai-quan Liu ◽  
Guang-yu Zhou ◽  
De-tian Li

Abstract Background and Aims With the continuous development and optimization of dialysis membrane materials, polysulfone (PS) as the third generation of dialysis membrane has replaced cellulose triacetate (CTA) and dominated the market because of its better biocompatibility. However, we found that the hypersensitivity to PS could be remitted by the application of CTA in clinical practice. Objective to compare the differences in toxin removal, hematological change and biocompatibility in maintenance hemodialysis (MHD) patients using CTA dialyzer and PS dialyzer. Method A total of 20 MHD patients treated in the Second Blood Purification Center of Shengjing Hospital from June 2017 to September 2017 were enrolled in this study. They were randomly divided into group CTA and group PS (n=10/each group). They were treated with regular hemodialysis of 4 hours/time and 3 times/week for one month. The clearances of creatinine (CR), blood urea nitrogen (BUN) and serum phosphorus (P), the changes of hemoglobin (Hb), platelet (PLT) and white blood cell (WBC), and the differences of C-reactive protein (CRP), IgE, complement 3 (C3), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were compared between group CTA and group PS. Results Age (t=-0.735, P=0.465), gender (c2 =2.410, P=0.120), dialysis age (t=0.336, P=0.738) and primary diseases (c2 =3.817, P=0.701) had no statistical differences between the two groups. Before the hemodialysis with CTA dialyzer and PS dialyzer, there were no statistical differences in all of the parameters between the two groups (P&gt;0.05). After application of CTA dialyzer and PS dialyzer for one month, ①there were no statistical differences in CR, BUN and P, nor in the changes of the above indicators between the two groups (P&gt;0.05); ② there was a statistical difference in Hb change between the two groups (t=-2.282, P=0.027), with better improvement of anemia in group CTA; ③ there was a statistical difference in PLT (t=2.947, P=0.005) between the two groups, with slighter change in group CTA than in group PS (t= 2.219, P=0.031); ④there were no statistical significances in WBC, VCAM-1, ICAM-1, IgE, CRP and C3 between the two groups (P&gt;0.05). Conclusion ①There were no significant difference in the clearances of small molecule toxins between CTA dialyzer and PS dialyzer. ② CTA was better than PS in the improvement of anemia. ③ The effect on PLT was less in group CTA than in group PS. ④ There were no significant differences in biocompatibility between CTA dialyzer and PS dialyzer.


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