World journal of stem cells最新文献

{"title":"Mechanism of adipose-derived mesenchymal stem cell exosomes in the treatment of heart failure.","authors":"Lei Wang,&nbsp;Jin-Jin Zhang,&nbsp;Sha-Sha Wang,&nbsp;Liang Li","doi":"10.4252/wjsc.v15.i9.897","DOIUrl":"10.4252/wjsc.v15.i9.897","url":null,"abstract":"<p><strong>Background: </strong>Heart failure (HF) is a global health problem characterized by impaired heart function. Cardiac remodeling and cell death contribute to the development of HF. Although treatments such as digoxin and angiotensin receptor blocker drugs have been used, their effectiveness in reducing mortality is uncertain. Researchers are exploring the use of adipose-derived mesenchymal stem cell (ADMSC) exosomes (Exos) as a potential therapy for HF. These vesicles, secreted by cells, may aid in tissue repair and regulation of inflammation and immune responses. However, further investigation is needed to understand the specific role of these vesicles in HF treatment.</p><p><strong>Aim: </strong>To investigate the mechanism of extracellular vesicles produced by ADMSC s in the treatment of HF.</p><p><strong>Methods: </strong>Exogenous surface markers of ADMSCs were found, and ADMSCs were cultured.</p><p><strong>Results: </strong>The identification of surface markers showed that the surface markers CD44 and CD29 of adipose-derived stem cells (ADSCs) were well expressed, while the surface markers CD45 and CD34 of ADSCs were negative, so the cultured cells were considered ADSCs. Western blotting detected the Exo surface marker protein, which expressed CD63 protein but did not express calnexin protein, indicating that ADSC-derived Exos were successfully extracted.</p><p><strong>Conclusion: </strong>The secretion of MSCs from adipose tissue can increase ATP levels, block cardiomyocyte apoptosis, and enhance the heart function of animals susceptible to HF. The inhibition of Bax, caspase-3 and p53 protein expression may be related to this process.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10600745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71414087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiomics reveal human umbilical cord mesenchymal stem cells improving acute lung injury <i>via</i> the lung-gut axis.","authors":"Lu Lv, En-Hai Cui, Bin Wang, Li-Qin Li, Feng Hua, Hua-Dong Lu, Na Chen, Wen-Yan Chen","doi":"10.4252/wjsc.v15.i9.908","DOIUrl":"10.4252/wjsc.v15.i9.908","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Acute lung injury (ALI) and its final severe stage, acute respiratory distress syndrome, are associated with high morbidity and mortality rates in patients due to the lack of effective specific treatments. Gut microbiota homeostasis, including that in ALI, is important for human health. Evidence suggests that the gut microbiota improves lung injury through the lung-gut axis. Human umbilical cord mesenchymal cells (HUC-MSCs) have attractive prospects for ALI treatment. This study hypothesized that HUC-MSCs improve ALI &lt;i&gt;via&lt;/i&gt; the lung-gut microflora.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;To explore the effects of HUC-MSCs on lipopolysaccharide (LPS)-induced ALI in mice and the involvement of the lung-gut axis in this process.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;C57BL/6 mice were randomly divided into four groups (18 rats per group): Sham, sham + HUC-MSCs, LPS, and LPS + HUC-MSCs. ALI was induced in mice by intraperitoneal injections of LPS (10 mg/kg). After 6 h, mice were intervened with 0.5 mL phosphate buffered saline (PBS) containing 1 × 10&lt;sup&gt;6&lt;/sup&gt; HUC-MSCs by intraperitoneal injections. For the negative control, 100 mL 0.9% NaCl and 0.5 mL PBS were used. Bronchoalveolar lavage fluid (BALF) was obtained from anesthetized mice, and their blood, lungs, ileum, and feces were obtained by an aseptic technique following CO&lt;sub&gt;2&lt;/sub&gt; euthanasia. Wright's staining, enzyme-linked immunosorbent assay, hematoxylin-eosin staining, Evans blue dye leakage assay, immunohistochemistry, fluorescence &lt;i&gt;in situ&lt;/i&gt; hybridization, western blot, 16S rDNA sequencing, and non-targeted metabolomics were used to observe the effect of HUC-MSCs on ALI mice, and the involvement of the lung-gut axis in this process was explored. One-way analysis of variance with post-hoc Tukey's test, independent-sample Student's &lt;i&gt;t&lt;/i&gt;-test, Wilcoxon rank-sum test, and Pearson correlation analysis were used for statistical analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;HUC-MSCs were observed to improve pulmonary edema and lung and ileal injury, and decrease mononuclear cell and neutrophil counts, protein concentrations in BALF and inflammatory cytokine levels in the serum, lung, and ileum of ALI mice. Especially, HUC-MSCs decreased Evans blue concentration and Toll-like receptor 4, myeloid differentiation factor 88, p-nuclear factor kappa-B (NF-κB)/NF-κB, and p-inhibitor α of NF-κB (p-IκBα)/IκBα expression levels in the lung, and raised the pulmonary vascular endothelial-cadherin, zonula occludens-1 (ZO-1), and occludin levels and ileal ZO-1, claudin-1, and occludin expression levels. HUC-MSCs improved gut and BALF microbial homeostases. The number of pathogenic bacteria decreased in the BALF of ALI mice treated with HUC-MSCs. Concurrently, the abundances of &lt;i&gt;Oscillospira&lt;/i&gt; and &lt;i&gt;Coprococcus&lt;/i&gt; in the feces of HUS-MSC-treated ALI mice were significantly increased. In addition, &lt;i&gt;Lactobacillus&lt;/i&gt;, &lt;i&gt;Bacteroides&lt;/i&gt;, and &lt;i&gt;unidentified_Rikenellaceae&lt;/i&gt; ge","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10600741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71414088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrin beta 3-overexpressing mesenchymal stromal cells display enhanced homing and can reduce atherosclerotic plaque.","authors":"Hai-Juan Hu,&nbsp;Xue-Ru Xiao,&nbsp;Tong Li,&nbsp;De-Min Liu,&nbsp;Xue Geng,&nbsp;Mei Han,&nbsp;Wei Cui","doi":"10.4252/wjsc.v15.i9.931","DOIUrl":"https://doi.org/10.4252/wjsc.v15.i9.931","url":null,"abstract":"<p><strong>Background: </strong>Umbilical cord (UC) mesenchymal stem cell (MSC) transplantation is a potential therapeutic intervention for atherosclerotic vascular disease. Integrin beta 3 (ITGB3) promotes cell migration in several cell types. However, whether ITGB-modified MSCs can migrate to plaque sites <i>in vivo</i> and play an anti-atherosclerotic role remains unclear.</p><p><strong>Aim: </strong>To investigate whether ITGB3-overexpressing MSCs (MSCs^ITGB3) would exhibit improved homing efficacy in atherosclerosis.</p><p><strong>Methods: </strong>UC MSCs were isolated and expanded. Lentiviral vectors encoding ITGB3 or green fluorescent protein (GFP) as control were transfected into MSCs. Sixty male apolipoprotein E^-/- mice were acquired from Beijing Vital River Lab Animal Technology Co., Ltd and fed with a high-fat diet (HFD) for 12 wk to induce the formation of atherosclerotic lesions. These HFD-fed mice were randomly separated into three clusters. GFP-labeled MSCs (MSCs^GFP) or MSCs^ITGB3 were transplanted into the mice intravenously <i>via</i> the tail vein. Immunofluorescence staining, Oil red O staining, histological analyses, western blotting, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction were used for the analyses.</p><p><strong>Results: </strong>ITGB3 modified MSCs successfully differentiated into the \"osteocyte\" and \"adipocyte\" phenotypes and were characterized by positive expression (> 91.3%) of CD29, CD73, and CD105 and negative expression (< 1.35%) of CD34 and Human Leukocyte Antigen-DR. In a transwell assay, MSCs^ITGB3 showed significantly faster migration than MSCs^GFP. ITGB3 overexpression had no effects on MSC viability, differentiation, and secretion. Immunofluorescence staining revealed that ITGB3 overexpression substantially enhanced the homing of MSCs to plaque sites. Oil red O staining and histological analyses further confirmed the therapeutic effects of MSCs^ITGB3, significantly reducing the plaque area. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction revealed that MSC^ITGB3 transplantation considerably decreased the inflammatory response in pathological tissues by improving the dynamic equilibrium of pro- and anti-inflammatory cytokines.</p><p><strong>Conclusion: </strong>These results showed that ITGB3 overexpression enhanced the MSC homing ability, providing a potential approach for MSC delivery to plaque sites, thereby optimizing their therapeutic effects.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10600744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71414085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced wound healing and hemostasis with exosome-loaded gelatin sponges from human umbilical cord mesenchymal stem cells.","authors":"Xin-Mei Hu,&nbsp;Can-Can Wang,&nbsp;Yu Xiao,&nbsp;Peng Jiang,&nbsp;Yu Liu,&nbsp;Zhong-Quan Qi","doi":"10.4252/wjsc.v15.i9.947","DOIUrl":"https://doi.org/10.4252/wjsc.v15.i9.947","url":null,"abstract":"<p><strong>Background: </strong>Rapid wound healing remains a pressing clinical challenge, necessitating studies to hasten this process. A promising approach involves the utilization of human umbilical cord mesenchymal stem cells (hUC-MSCs) derived exosomes. The hypothesis of this study was that these exosomes, when loaded onto a gelatin sponge, a common hemostatic material, would enhance hemostasis and accelerate wound healing.</p><p><strong>Aim: </strong>To investigate the hemostatic and wound healing efficacy of gelatin sponges loaded with hUC-MSCs-derived exosomes.</p><p><strong>Methods: </strong>Ultracentrifugation was used to extract exosomes from hUC-MSCs. Nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and western blot techniques were used to validate the exosomes. <i>In vitro</i> experiments were performed using L929 cells to evaluate the cytotoxicity of the exosomes and their impact on cell growth and survival. New Zealand rabbits were used for skin irritation experiments to assess whether they caused adverse skin reactions. Hemolysis test was conducted using a 2% rabbit red blood cell suspension to detect whether they caused hemolysis. Moreover, <i>in vivo</i> experiments were carried out by implanting a gelatin sponge loaded with exosomes subcutaneously in Sprague-Dawley (SD) rats to perform biocompatibility tests. In addition, coagulation index test was conducted to evaluate their impact on blood coagulation. Meanwhile, SD rat liver defect hemostasis model and full-thickness skin defect model were used to study whether the gelatin sponge loaded with exosomes effectively stopped bleeding and promoted wound healing.</p><p><strong>Results: </strong>The NTA, TEM, and western blot experimental results confirmed that exosomes were successfully isolated from hUC-MSCs. The gelatin sponge loaded with exosomes did not exhibit significant cell toxicity, skin irritation, or hemolysis, and they demonstrated good compatibility in SD rats. Additionally, the effectiveness of the gelatin sponge loaded with exosomes in hemostasis and wound healing was validated. The results of the coagulation index experiment indicated that the gelatin sponge loaded with exosomes had significantly better coagulation effect compared to the regular gelatin sponge, and they showed excellent hemostatic performance in a liver defect hemostasis model. Finally, the full-thickness skin defect healing experiment results showed significant improvement in the healing process of wounds treated with the gelatin sponge loaded with exosomes compared to other groups.</p><p><strong>Conclusion: </strong>Collectively, the gelatin sponge loaded with hUC-MSCs-derived exosomes is safe and efficacious for promoting hemostasis and accelerating wound healing, warranting further clinical application.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10600743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71414084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wnt signaling pathway inhibitor promotes mesenchymal stem cells differentiation into cardiac progenitor cells <i>in vitro</i> and improves cardiomyopathy <i>in vivo</i>.","authors":"Rabbia Muneer,&nbsp;Rida-E-Maria Qazi,&nbsp;Abiha Fatima,&nbsp;Waqas Ahmad,&nbsp;Asmat Salim,&nbsp;Luciana Dini,&nbsp;Irfan Khan","doi":"10.4252/wjsc.v15.i8.821","DOIUrl":"https://doi.org/10.4252/wjsc.v15.i8.821","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular diseases particularly myocardial infarction (MI) are the leading cause of mortality and morbidity around the globe. As cardiac tissue possesses very limited regeneration potential, therefore use of a potent small molecule, inhibitor Wnt production-4 (IWP-4) for stem cell differentiation into cardiomyocytes could be a promising approach for cardiac regeneration. Wnt pathway inhibitors may help stem cells in their fate determination towards cardiomyogenic lineage and provide better homing and survival of cells <i>in vivo</i>. Mesenchymal stem cells (MSCs) derived from the human umbilical cord have the potential to regenerate cardiac tissue, as they are easy to isolate and possess multilineage differentiation capability. IWP-4 may promote the differentiation of MSCs into the cardiac lineage.</p><p><strong>Aim: </strong>To evaluate the cardiac differentiation ability of IWP-4 and its subsequent <i>in vivo</i> effects.</p><p><strong>Methods: </strong>Umbilical cord tissue of human origin was utilized to isolate the MSCs which were characterized by their morphology, immunophenotyping of surface markers specific to MSCs, as well as by tri-lineage differentiation capability. Cytotoxicity analysis was performed to identify the optimal concentration of IWP-4. MSCs were treated with 5 μM IWP-4 at two different time intervals. Differentiation of MSCs into cardiomyocytes was evaluated at DNA and protein levels. The MI rat model was developed. IWP-4 treated as well as untreated MSCs were implanted in the MI model, then the cardiac function was analyzed <i>via</i> echocardiography. MSCs were labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) dye for tracking, while the regeneration of infarcted myocardium was examined by histology and immunohistochemistry.</p><p><strong>Results: </strong>MSCs were isolated and characterized. Cytotoxicity analysis showed that IWP-4 was non-cytotoxic at 5 μM concentration. Cardiac specific gene and protein expression analyses exhibited more remarkable results in fourteen days treated group that was eventually selected for <i>in vivo</i> transplantation. Cardiac function was restored in the IWP-4 treated group in comparison to the MI group. Immunohistochemical analysis confirmed the homing of pre-differentiated MSCs that were labeled with DiI cell labeling dye. Histological analysis confirmed the significant reduction in fibrotic area, and improved left ventricular wall thickness in IWP-4 treated MSC group.</p><p><strong>Conclusion: </strong>Treatment of MSCs with IWP-4 inhibits Wnt pathway and promotes cardiac differentiation. These pre-conditioned MSCs transplanted <i>in vivo</i> improved cardiac function by cell homing, survival, and differentiation at the infarcted region, increased left ventricular wall thickness, and reduced infarct size.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/35/WJSC-15-821.PMC10494566.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10243989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Constitutive aryl hydrocarbon receptor facilitates the regenerative potential of mouse bone marrow mesenchymal stromal cells.","authors":"Jing Huang,&nbsp;Yi-Ning Wang,&nbsp;Yi Zhou","doi":"10.4252/wjsc.v15.i8.807","DOIUrl":"https://doi.org/10.4252/wjsc.v15.i8.807","url":null,"abstract":"<p><strong>Background: </strong>Bone marrow mesenchymal stromal cells (BMSCs) are the commonly used seed cells in tissue engineering. Aryl hydrocarbon receptor (AhR) is a transcription factor involved in various cellular processes. However, the function of constitutive AhR in BMSCs remains unclear.</p><p><strong>Aim: </strong>To investigate the role of AhR in the osteogenic and macrophage-modulating potential of mouse BMSCs (mBMSCs) and the underlying mechanism.</p><p><strong>Methods: </strong>Immunochemistry and immunofluorescent staining were used to observe the expression of AhR in mouse bone marrow tissue and mBMSCs. The overexpression or knockdown of AhR was achieved by lentivirus-mediated plasmid. The osteogenic potential was observed by alkaline phosphatase and alizarin red staining. The mRNA and protein levels of osteogenic markers were detected by quantitative polymerase chain reaction (qPCR) and western blot. After coculture with different mBMSCs, the cluster of differentiation (CD) 86 and CD206 expressions levels in RAW 264.7 cells were analyzed by flow cytometry. To explore the underlying molecular mechanism, the interaction of AhR with signal transducer and activator of transcription 3 (STAT3) was observed by co-immunoprecipitation and phosphorylation of STAT3 was detected by western blot.</p><p><strong>Results: </strong>AhR expressions in mouse bone marrow tissue and isolated mBMSCs were detected. AhR overexpression enhanced the osteogenic potential of mBMSCs while AhR knockdown suppressed it. The ratio of CD86+ RAW 264.7 cells cocultured with AhR-overexpressed mBMSCs was reduced and that of CD206+ cells was increased. AhR directly interacted with STAT3. AhR overexpression increased the phosphorylation of STAT3. After inhibition of STAT3 <i>via</i> stattic, the promotive effects of AhR overexpression on the osteogenic differentiation and macrophage-modulating were partially counteracted.</p><p><strong>Conclusion: </strong>AhR plays a beneficial role in the regenerative potential of mBMSCs partially by increasing phosphorylation of STAT3.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/91/62/WJSC-15-807.PMC10494570.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10239160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon-gamma and tumor necrosis factor-alpha synergistically enhance the immunosuppressive capacity of human umbilical-cord-derived mesenchymal stem cells by increasing PD-L1 expression.","authors":"Zhuo Chen,&nbsp;Meng-Wei Yao,&nbsp;Zhi-Lin Shen,&nbsp;Shi-Dan Li,&nbsp;Wei Xing,&nbsp;Wei Guo,&nbsp;Zhan Li,&nbsp;Xiao-Feng Wu,&nbsp;Luo-Quan Ao,&nbsp;Wen-Yong Lu,&nbsp;Qi-Zhou Lian,&nbsp;Xiang Xu,&nbsp;Xiang Ao","doi":"10.4252/wjsc.v15.i8.787","DOIUrl":"https://doi.org/10.4252/wjsc.v15.i8.787","url":null,"abstract":"<p><strong>Background: </strong>The immunosuppressive capacity of mesenchymal stem cells (MSCs) is dependent on the \"license\" of several proinflammatory factors to express immunosuppressive factors such as programmed cell death 1 ligand 1 (PD-L1), which determines the clinical therapeutic efficacy of MSCs for inflammatory or immune diseases. In MSCs, interferon-gamma (IFN-γ) is a key inducer of PD-L1 expression, which is synergistically enhanced by tumor necrosis factor-alpha (TNF-α); however, the underlying mechanism is unclear.</p><p><strong>Aim: </strong>To reveal the mechanism of pretreated MSCs express high PD-L1 and explore the application of pretreated MSCs in ulcerative colitis.</p><p><strong>Methods: </strong>We assessed PD-L1 expression in human umbilical-cord-derived MSCs (hUC-MSCs) induced by IFN-γ and TNF-α, alone or in combination. Additionally, we performed signal pathway inhibitor experiments as well as RNA interference experiments to elucidate the molecular mechanism by which IFN-γ alone or in combination with TNF-α induces PD-L1 expression. Moreover, we used luciferase reporter gene experiments to verify the binding sites of the transcription factors of each signal transduction pathway to the targeted gene promoters. Finally, we evaluated the immunosuppressive capacity of hUC-MSCs treated with IFN-γ and TNF-α in both an <i>in vitro</i> mixed lymphocyte culture assay, and <i>in vivo</i> in mice with dextran sulfate sodium-induced acute colitis.</p><p><strong>Results: </strong>Our results suggest that IFN-γ induction alone upregulates PD-L1 expression in hUC-MSCs while TNF-α alone does not, and that the co-induction of IFN-γ and TNF-α promotes higher expression of PD-L1. IFN-γ induces hUC-MSCs to express PD-L1, in which IFN-γ activates the JAK/STAT1 signaling pathway, up-regulates the expression of the interferon regulatory factor 1 (IRF1) transcription factor, promotes the binding of IRF1 and the PD-L1 gene promoter, and finally promotes PD-L1 mRNA. Although TNF-α alone did not induce PD-L1 expression in hUC-MSCs, the addition of TNF-α significantly enhanced IFN-γ-induced JAK/STAT1/IRF1 activation. TNF-α up-regulated IFN-γ receptor expression through activation of the nuclear factor kappa-B signaling pathway, which significantly enhanced IFN-γ signaling. Finally, co-induced hUC-MSCs have a stronger inhibitory effect on lymphocyte proliferation, and significantly ameliorate weight loss, mucosal damage, inflammatory cell infiltration, and up-regulation of inflammatory factors in colitis mice.</p><p><strong>Conclusion: </strong>Overall, our results suggest that IFN-γ and TNF-α enhance both the immunosuppressive ability of hUC-MSCs and their efficacy in ulcerative colitis by synergistically inducing high expression of PD-L1.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/29/a1/WJSC-15-787.PMC10494569.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10232121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin ameliorates oxidative stress-induced senescence in rat nucleus pulposus-derived mesenchymal stem cells <i>via</i> the miR-34a-5p/SIRT1 axis.","authors":"Wen-Jie Zhao,&nbsp;Xin Liu,&nbsp;Man Hu,&nbsp;Yu Zhang,&nbsp;Peng-Zhi Shi,&nbsp;Jun-Wu Wang,&nbsp;Xu-Hua Lu,&nbsp;Xiao-Fei Cheng,&nbsp;Yu-Ping Tao,&nbsp;Xin-Min Feng,&nbsp;Yong-Xiang Wang,&nbsp;Liang Zhang","doi":"10.4252/wjsc.v15.i8.842","DOIUrl":"https://doi.org/10.4252/wjsc.v15.i8.842","url":null,"abstract":"<p><strong>Background: </strong>Intervertebral disc degeneration (IDD) is a main contributor to low back pain. Oxidative stress, which is highly associated with the progression of IDD, increases senescence of nucleus pulposus-derived mesenchymal stem cells (NPMSCs) and weakens the differentiation ability of NPMSCs in degenerated intervertebral discs (IVDs). Quercetin (Que) has been demonstrated to reduce oxidative stress in diverse degenerative diseases.</p><p><strong>Aim: </strong>To investigate the role of Que in oxidative stress-induced NPMSC damage and to elucidate the underlying mechanism.</p><p><strong>Methods: </strong><i>In vitro</i>, NPMSCs were isolated from rat tails. Senescence-associated β-galactosidase (SA-β-Gal) staining, cell cycle, reactive oxygen species (ROS), real-time quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, and western blot analyses were used to evaluated the protective effects of Que. Meanwhile the relationship between miR-34a-5p and Sirtuins 1 (SIRT1) was evaluated by dual-luciferase reporter assay. To explore whether Que modulates tert-butyl hydroperoxide (TBHP)-induced senescence of NPMSCs <i>via</i> the miR-34a-5p/SIRT1 pathway, we used adenovirus vectors to overexpress and downregulate the expression of miR-34a-5p and used SIRT1 siRNA to knockdown SIRT1 expression. <i>In vivo,</i> a puncture-induced rat IDD model was constructed, and X rays and histological analysis were used to assess whether Que could alleviate IDD <i>in vivo</i>.</p><p><strong>Results: </strong>We found that TBHP can cause NPMSCs senescence changes, such as reduced cell proliferation ability, increased SA-β-Gal activity, cell cycle arrest, the accumulation of ROS, and increased expression of senescence-related proteins. While abovementioned senescence indicators were significantly alleviated by Que treatment. Que decreased the expression levels of senescence-related proteins (p16, p21, and p53) and senescence-associated secreted phenotype (SASP), including IL-1β, IL-6, and MMP-13, and it increased the expression of SIRT1. In addition, the protective effects of Que on cell senescence were partially reversed by miR-34a-5p overexpression and SIRT1 knockdown. <i>In vivo</i>, X-ray, and histological analyses indicated that Que alleviated IDD in a puncture-induced rat model.</p><p><strong>Conclusion: </strong>In summary, the present study provides evidence that Que reduces oxidative stress-induced senescence of NPMSCs <i>via</i> the miR-34a/SIRT1 signaling pathway, suggesting that Que may be a potential agent for the treatment of IDD.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9e/9f/WJSC-15-842.PMC10494568.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10239154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mastering the craft: Creating an insightful and widely-cited literature review.","authors":"Shengwen Calvin Li","doi":"10.4252/wjsc.v15.i8.781","DOIUrl":"https://doi.org/10.4252/wjsc.v15.i8.781","url":null,"abstract":"<p><p>The art of constructing an insightful literature review manuscript has witnessed an exemplar in the work of Oz <i>et al</i> (2023), wherein concept progression harmoniously merges with figures and tables. Reflecting on retrospective data science, it is evident that well-cited articles can wield a transformative influence on the Journal Citation Reports Impact Factor score, as exemplified by Robert Weinberg's landmark on cancer (Hanahan and Weinberg, 2011). Here, we aim to spotlight a commendable contribution by Tuba Oz, Ajeet Kaushik, and Małgorzata Kujawska in this issue while pivoting towards identifying the hallmarks of a subpar literature review-elements that hinder rather than promote advancement. The hurdles and roadblocks encountered within subpar literature reviews are multifold. Anticipation of emerging trends, identification of challenges, and exploration of solutions remain conspicuously absent. Original Contributions fail to surface amidst the vast sea of pre-existing literature, with noticeable gaps amplified by the lack of illustrative figures and tables. The manuscript, at times, assumes a skeletal form, reflecting an attempt to accommodate an excess of references, leading to convoluted sentences laden with citations. In contrast, a potent solution lies in adopting a comprehensive approach. A nuanced and critical evaluation of sources can culminate in a robust discussion, surpassing the mere summarization of conclusions drawn by others. This approach, often dismissed, holds the potential to elevate clarity, coherence, and logical flow, ultimately inviting engaged readership and coveted citations. The critical necessity of integrating visionary insights is underscored and achieved through a rigorous analysis of pivotal concepts and innovative ideas. Examples can be harnessed to elucidate the application of these solutions. We advocate a paradigm shift, urging literature review writers to embrace the readers' perspective. A literature review's purpose extends beyond providing a comprehensive panorama; it should illuminate avenues for concept development within a specific field of interest. By achieving this balance, literature reviews stand to captivate a devoted readership, paving the way for manuscripts that are both widely read and frequently cited. The pathway forward requires a fusion of astute analysis and visionary insights, shaping the future of literature review composition.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f9/48/WJSC-15-781.PMC10494571.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10239153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Up-to-date meta-analysis of long-term evaluations of mesenchymal stem cell therapy for complex perianal fistula.","authors":"Fang Cheng, Huang Zhong, Zhong Huang, Zhi Li","doi":"10.4252/wjsc.v15.i8.866","DOIUrl":"10.4252/wjsc.v15.i8.866","url":null,"abstract":"<p><strong>Background: </strong>Local mesenchymal stem cell (MSC) therapy for complex perianal fistulas (PFs) has shown considerable promise. But, the long-term safety and efficacy of MSC therapy in complex PFs remain unknown.</p><p><strong>Aim: </strong>To explore the long-term effectiveness and safety of local MSC therapy for complex PFs.</p><p><strong>Methods: </strong>Sources included the PubMed, EMBASE, and Cochrane Library databases. A standard meta-analysis was performed using RevMan 5.3.</p><p><strong>Results: </strong>After screening, 6 studies met the inclusion criteria. MSC therapy was associated with an improved long-term healing rate (HR) compared with the control condition [odds ratio (OR) = 2.13; 95% confidence interval (95%CI): 1.34 to 3.38; <i>P</i> = 0.001]. Compared with fibrin glue (FG) therapy alone, MSC plus FG therapy was associated with an improved long-term HR (OR = 2.30; 95%CI: 1.21 to 4.36; <i>P</i> = 0.01). When magnetic resonance imaging was used to evaluate fistula healing, MSC therapy was found to achieve a higher long-term HR than the control treatment (OR = 2.79; 95%CI: 1.37 to 5.67; <i>P</i> = 0.005). There were no significant differences in long-term safety (OR = 0.77; 95%CI: 0.27 to 2.24; <i>P</i> = 0.64).</p><p><strong>Conclusion: </strong>Our study indicated that local MSC therapy promotes long-term and sustained healing of complex PFs and that this method is safe.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/60/04/WJSC-15-866.PMC10494567.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10243996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}