Qun Qian, N. Zhu, Wenzhe Li, Songlin Wan, Dongcheng Wu, Yun-hua Wu, Weicheng Liu
{"title":"Human Umbilical Mesenchymal Stem Cells-Derived Microvesicles Attenuate Formation of Hypertrophic Scar through Multiple Mechanisms","authors":"Qun Qian, N. Zhu, Wenzhe Li, Songlin Wan, Dongcheng Wu, Yun-hua Wu, Weicheng Liu","doi":"10.1155/2023/9125265","DOIUrl":"https://doi.org/10.1155/2023/9125265","url":null,"abstract":"Mesenchymal stem cells and the derived extracellular microvesicles are potential promising therapy for many disease conditions, including wound healing. Since current therapeutic approaches do not satisfactorily attenuate or ameliorate formation of hypertrophic scars, it is necessary to develop novel drugs to achieve better outcomes. In this study, we investigated the effects and the underlying mechanisms of human umbilical mesenchymal stem cells (HUMSCs)-derived microvesicles (HUMSCs-MVs) on hypertrophic scar formation using a rabbit ear model and a human foreskin fibroblasts (HFF) culture model. The results showed that HUMSCs-MVs reduced formation of hypertrophic scar tissues in the rabbit model based on appearance observation, and hematoxylin and eosin (H&E), Masson, and immunohistochemical stainings. HUMSCs-MVs inhibited invasion of HFF cells and decreased the levels of the α-SMA, N-WASP, and cortacin proteins. HUMSCs-MVs also inhibited cell proliferation of HFF cells. The MMP-1, MMP-3, and TIMP-3 mRNA levels were significantly increased, and the TIMP-4 mRNA level and the NF-kB p65/β-catenin protein levels were significantly decreased in HFF cells after HUMSCs-MVs treatment. The p-SMAD2/3 levels and the ratios of p-SMAD2/3/SMAD2/3 were significantly decreased in both the wound healing tissues and HFF cells after HUMSCs-MVs treatment. CD34 levels were significantly decreased in both wound healing scar tissues and HFF cells after HUMSCs-MVs treatment. The VEGF-A level was also significantly decreased in HFF cells after HUMSCs-MVs treatment. The magnitudes of changes in these markers by HUMSCs-MVs were mostly higher than those by dexamethasone. These results suggested that HUMSCs-MVs attenuated formation of hypertrophic scar during wound healing through inhibiting proliferation and invasion of fibrotic cells, inflammation and oxidative stress, Smad2/3 activation, and angiogenesis. HUMSCs-MVs is a potential promising drug to attenuate formation of hypertrophic scar during wound healing.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44281132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Factors Associated with 28-day Critical Illness Development During the First Wave of COVID-19.","authors":"Uluhan Sili, Pınar Ay, Hüseyin Bilgin, Ahmet Topuzoğlu, Elif Tükenmez-Tigen, Buket Ertürk-Şengel, Dilek Yağçı-Çağlayık, Baran Balcan, Derya Kocakaya, Şehnaz Olgun-Yıldızeli, Fethi Gül, Beliz Bilgili, Rabia Can-Sarınoğlu, Ayşegül Karahasan-Yağcı, Lütfiye Mülazimoğlu-Durmuşoğlu, Emel Eryüksel, Zekaver Odabaşı, Haner Direskeneli, Sait Karakurt, Volkan Korten","doi":"10.36519/idcm.2023.206","DOIUrl":"10.36519/idcm.2023.206","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to define the predictors of critical illness development within 28 days postadmission during the first wave of the COVID-19 pandemic.</p><p><strong>Materials and methods: </strong>We conducted a prospective cohort study including 477 PCR-positive COVID-19 patients admitted to a tertiary care hospital in Istanbul from March 12 to May 12, 2020.</p><p><strong>Results: </strong>The most common presenting symptoms were cough, dyspnea, and fatigue. Critical illness developed in 45 (9.4%; 95% CI=7.0%-12.4%) patients. In the multivariable analysis, age (hazard ratio (HR)=1.05, <i>p</i><0.001), number of comorbidities (HR=1.33, <i>p</i>=0.02), procalcitonin ≥0.25 µg/L (HR=2.12, <i>p</i>=0.03) and lactate dehydrogenase (LDH) ≥350 U/L (HR=2.04, <i>p</i>=0.03) were independently associated with critical illness development. The World Health Organization (WHO) ordinal scale for clinical improvement on admission was the strongest predictor of critical illness (HR=4.15, <i>p</i><0.001). The patients hospitalized at the end of the study period had a much better prognosis compared to the patients hospitalized at the beginning (HR=0.14; <i>p</i>=0.02). The C-index of the model was 0.92.</p><p><strong>Conclusion: </strong>Age, comorbidity number, the WHO scale, LDH, and procalcitonin were independently associated with critical illness development. Mortality from COVID-19 seemed to be decreasing as the first wave of the pandemic advanced.</p><p><strong>Graphic abstract: </strong>Graphic Abstract.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2016 1","pages":"94-105"},"PeriodicalIF":0.0,"publicationDate":"2023-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86383685","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":"Comparison of Biological Properties and Clinical Application of Mesenchymal Stem Cells from the Mesoderm and Ectoderm.","authors":"Zhenning Wang, Meng Huang, Yu Zhang, Xiaoxia Jiang, Lulu Xu","doi":"10.1155/2023/4547875","DOIUrl":"10.1155/2023/4547875","url":null,"abstract":"<p><p>Since the discovery of mesenchymal stem cells (MSCs) in the 1970s, they have been widely used in the treatment of a variety of diseases because of their wide sources, strong differentiation potential, rapid expansion in vitro, low immunogenicity, and so on. At present, most of the related research is on mesoderm-derived MSCs (M-MSCs) such as bone marrow MSCs and adipose-derived MSCs. As a type of MSC, ectoderm-derived MSCs (E-MSCs) have a stronger potential for self-renewal, multidirectional differentiation, and immunomodulation and have more advantages than M-MSCs in some specific conditions. This paper analyzes the relevant research development of E-MSCs compared with that of M-MSCs; summarizes the extraction, discrimination and culture, biological characteristics, and clinical application of E-MSCs; and discusses the application prospects of E-MSCs. This summary provides a theoretical basis for the better application of MSCs from both ectoderm and mesoderm in the future.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2023 ","pages":"4547875"},"PeriodicalIF":4.3,"publicationDate":"2023-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10276766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9653931","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}
Stem Cells InternationalPub Date : 2023-04-29eCollection Date: 2023-01-01DOI: 10.1155/2023/9997676
Yang Yang, Yueyuan Chen, Jiajia Liu, Bo Zhang, Linlin Yang, Jianhua Xue, Zexu Zhang, Lili Qin, Rongpeng Bian
{"title":"MiR-125b-5p/STAT3 Axis Regulates Drug Resistance in Osteosarcoma Cells by Acting on ABC Transporters.","authors":"Yang Yang, Yueyuan Chen, Jiajia Liu, Bo Zhang, Linlin Yang, Jianhua Xue, Zexu Zhang, Lili Qin, Rongpeng Bian","doi":"10.1155/2023/9997676","DOIUrl":"10.1155/2023/9997676","url":null,"abstract":"<p><strong>Background: </strong>The poor prognosis of the highly malignant tumor osteosarcoma stems from its drug resistance and therefore exploring its resistance mechanisms will help us identify more effective treatment options. However, the effects of miR-125b-5p on drug resistance in osteosarcoma cells are still unclear.</p><p><strong>Methods: </strong>To study the effects of miR-125b-5p on drug resistance in osteosarcoma cells. Osteosarcoma-resistant miR-125b-5p was obtained from the databases GeneCards and g:Profiler. CCK8, western blot, and transwell were applied for the detection of the miR-125b-5p effects on proliferation, migration, invasion, apoptosis, and drug resistance in osteosarcoma. Bioinformatics is aimed at demonstrating the targeting factor miR-125b-5p, performing protein interaction enrichment analysis by Metascape, and finally validating by binding sites.</p><p><strong>Results: </strong>Upregulation of miR-125b-5p restrains proliferation, migration, and invasion of osteosarcoma and promotes apoptosis. In addition, miR-125b-5p can restore drug sensitivity in drug-resistant osteosarcoma. miR-125-5p restrains the signal transducer and inhibits the transcription 3 (STAT3) expression activator via targeting its 3'-UTR. STAT3 affects drug-resistant osteosarcoma to regulate the ABC transporter.</p><p><strong>Conclusion: </strong>miR-125b-5p/STAT3 axis mediates the drug resistance of osteosarcoma by acting on ABC transporter.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2023 ","pages":"9997676"},"PeriodicalIF":4.3,"publicationDate":"2023-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10163973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9813282","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}
Yang Liu, Lin Yang, Hao Liang, Jianhua Zeng, Yuanyuan Hua, Huancheng Wu
{"title":"Construction of an Excellent 7 mRNAsi-Related Gene Model Based on Cancer Stem Cells for Predicting Survival Outcome of Cervical Cancer","authors":"Yang Liu, Lin Yang, Hao Liang, Jianhua Zeng, Yuanyuan Hua, Huancheng Wu","doi":"10.1155/2023/8383058","DOIUrl":"https://doi.org/10.1155/2023/8383058","url":null,"abstract":"Background. Cervical cancer (CC) is one of the most frequent female malignancy. Cancer stem cells (CSCs) positively affect survival outcomes in cancer patients, but in cervical cancer, the mechanism of tumor stem cells is still uncertain. Methods. RNA-seq data and related clinical follow-up of patients suffering from CC were from TCGA. Consensus clustering screened prognostic mRNAsi-related genes and identified molecular subtypes for CC. Based on the overlapping differentially expressed genes (DEGs) in subtypes, we employed LASSO and multivariate Cox regression to screen prognostic-related genes and established the RiskScore system. The patients were grouped by RiskScore, the prognosis was analyzed by the Kaplan-Meier (K-M) curve among the various groups, and the precision of the RiskScore was assessed by the ROC curve. Finally, the potential worth of RiskScore in immunotherapy/chemotherapy response was assessed by evaluating TIDE scores and chemotherapy drug \u0000 \u0000 \u0000 \u0000 IC\u0000 \u0000 \u0000 50\u0000 \u0000 \u0000 \u0000 values. Results. We noticed that patients with low mRNAsi had a shorter survival and then identified three molecular subtypes (C1-3), with the C1 having the worst prognosis and the lowest mRNAsi. Finally, we identified 7 prognostic-related genes (SPRY4, PPP1R14A, MT1A, DES, SEZ6L2, SLC22A3, and CXCL8) via LASSO and Cox regression analysis. We established a 7-gene model defined RiskScore to predict the prognosis of CC patients. K-M curve indicated that low RiskScore patients had improved prognosis, and ROC curves indicated that RiskScore could precisely direct the prognostic evaluation for those suffering from the cancer. This was also confirmed in the GSE44001 and GSE52903 external cohorts. Patients were more sensitive to immunotherapy if with low RiskScore, and RiskScore exhibited precise assessment ability in predicting response to immunological therapy in CC patients. Conclusion. CC stemness is associated with patient prognosis, and the RiskScore constructed based on stemness characteristics is an independent prognostic index, which is expected to be a guide for immunotherapy, providing a new idea for CC clinical practice.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47513177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cells InternationalPub Date : 2023-03-30eCollection Date: 2023-01-01DOI: 10.1155/2023/1429642
Pingting Ye, Lei Feng, Dan Zhang, Ruihao Li, Yixuan Wen, Xiaohan Tong, Shuo Shi, Chunyan Dong
{"title":"Metformin Ameliorates D-Galactose-Induced Senescent Human Bone Marrow-Derived Mesenchymal Stem Cells by Enhancing Autophagy.","authors":"Pingting Ye, Lei Feng, Dan Zhang, Ruihao Li, Yixuan Wen, Xiaohan Tong, Shuo Shi, Chunyan Dong","doi":"10.1155/2023/1429642","DOIUrl":"10.1155/2023/1429642","url":null,"abstract":"<p><p>Human bone marrow-derived mesenchymal stem cells (hBMSCs) are promising candidates for stem cell therapy in clinical trials. Applications of hBMSCs in clinical therapy are limited by cellular senescence due to long-term <i>ex vivo</i> expansion. Metformin, an oral hypoglycemic drug for type 2 diabetes, has been shown to have antiaging effects. However, the mechanisms of metformin in antiaging treatment remain controversial. Here, we used D-galactose (D-gal) to establish an appropriate model of senescent hBMSCs to explore the antiaging effects of metformin. Following metformin treatment with a low concentration range, senescence phenotypes induced by D-gal significantly changed, including generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential (MMP), and cell cycle arrest. In contrast, no apparent change was found in unsenescent hBMSCs. Furthermore, the results show that activation of 5'AMP-activated protein kinase (AMPK) by metformin enhances cell autophagy in senescent hBMSCs. These findings suggest that metformin exerts antiaging function within the low concentration range by enhancing autophagy and exhibits potential benefits for clinical stem cell therapy by ameliorating the <i>ex vivo</i> replicative senescence of hBMSCs.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2023 ","pages":"1429642"},"PeriodicalIF":3.8,"publicationDate":"2023-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10079386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9327113","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}
Stem Cells InternationalPub Date : 2023-02-23eCollection Date: 2023-01-01DOI: 10.1155/2023/6245160
Yibo Ma, Shuo Zheng, Mingjun Xu, Changjian Chen, Hongtao He
{"title":"Establishing and Validating an Aging-Related Prognostic Signature in Osteosarcoma.","authors":"Yibo Ma, Shuo Zheng, Mingjun Xu, Changjian Chen, Hongtao He","doi":"10.1155/2023/6245160","DOIUrl":"10.1155/2023/6245160","url":null,"abstract":"<p><p>Aging is an inevitable process that biological changes accumulate with time and results in increased susceptibility to different tumors. But currently, aging-related genes (ARGs) in osteosarcoma were not clear. We investigated the potential prognostic role of ARGs and established an ARG-based prognostic signature for osteosarcoma. The transcriptome data and corresponding clinicopathological information of patients with osteosarcoma were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Molecular subtypes were generated based on prognosis-related ARGs obtained from univariate Cox analysis. With ARGs, a risk signature was built by univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Differences in clinicopathological features, immune infiltration, immune checkpoints, responsiveness to immunotherapy and chemotherapy, and biological pathways were assessed according to molecular subtypes and the risk signature. Based on risk signature and clinicopathological variables, a nomogram was established and validated. Three molecular subtypes with distinct clinical outcomes were classified based on 36 prognostic ARGs for osteosarcoma. A nine-ARG-based signature in the TCGA cohort, including <i>BMP8A</i>, <i>CORT</i>, <i>SLC17A9</i>, <i>VEGFA</i>, <i>GAL</i>, <i>SSX1</i>, <i>RASGRP2</i>, <i>SDC3</i>, and <i>EVI2B</i>, has been created and developed and could well perform patient stratification into the high- and low-risk groups. There were significant differences in clinicopathological features, immune checkpoints and infiltration, responsiveness to immunotherapy and chemotherapy, cancer stem cell, and biological pathways among the molecular subtypes. The risk signature and metastatic status were identified as independent prognostic factors for osteosarcoma. A nomogram combining ARG-based risk signature and metastatic status was established, showing great prediction accuracy and clinical benefit for osteosarcoma OS. We characterized three ARG-based molecular subtypes with distinct characteristics and built an ARG-based risk signature for osteosarcoma prognosis, which could facilitate prognosis prediction and making personalized treatment in osteosarcoma.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"1 1","pages":"6245160"},"PeriodicalIF":4.3,"publicationDate":"2023-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10643040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42242873","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}
Stem Cells InternationalPub Date : 2023-02-20eCollection Date: 2023-01-01DOI: 10.1155/2023/7441367
Chao Ren, Wei Yi, Bo Jiang, Erhe Gao, Jiali Liang, Bo Zhang, Zhe Yang, Dezhi Zheng, Yong Zhang
{"title":"Diminished AdipoR1/APPL1 Interaction Mediates Reduced Cardioprotective Actions of Adiponectin against Myocardial Ischemia/Reperfusion Injury in Type-2 Diabetic Mice.","authors":"Chao Ren, Wei Yi, Bo Jiang, Erhe Gao, Jiali Liang, Bo Zhang, Zhe Yang, Dezhi Zheng, Yong Zhang","doi":"10.1155/2023/7441367","DOIUrl":"10.1155/2023/7441367","url":null,"abstract":"<p><strong>Background: </strong>Obesity-related diseases have important implications for the occurrence, severity, and outcome of ischemic heart disease. Patients with obesity, hyperlipidemia, and diabetes mellitus (metabolic syndrome) are at increased risk of heart attack with decreased plasma lipocalin levels, and lipocalin is negatively correlated with heart attack incidence. APPL1 is a signaling protein with multiple functional structural domains and plays an important role in the APN signaling pathway. There are two known subtypes of lipocalin membrane receptors, AdipoR1 and AdipoR2. AdioR1 is mainly distributed in skeletal muscle while AdipoR2 is mainly distributed in the liver.</p><p><strong>Objective: </strong>To clarify whether the AdipoR1-APPL1 signaling pathway mediates the effect of lipocalin in reducing myocardial ischemia/reperfusion injury and its mechanism will provide us with a new approach to treat myocardial ischemia/reperfusion injury using lipocalin as an intervention and therapeutic target.</p><p><strong>Methods: </strong>(1) Induction of hypoxia/reoxygenation in SD mammary rat cardiomyocytes to simulate myocardial ischemia/reperfusion; (2) downregulation of APPL1 expression in cardiomyocytes to observe the effect of lipocalin on myocardial ischemia/reperfusion and its mechanism of action.</p><p><strong>Results: </strong>(1) Primary mammary rat cardiomyocytes were isolated and cultured and induced to simulate MI/R by hypoxia/reoxygenation; (2) lipocalin inhibited H/R-induced apoptosis in cardiomyocytes; and (3) APN attenuated MI/R injury through AdipoR1-APPL1 and the possible mechanism.</p><p><strong>Conclusion: </strong>This study demonstrates for the first time that lipocalin can attenuate myocardial ischemia/reperfusion injury through the AdipoR1-APPL1 signaling pathway and that the reduction of AdipoR1/APPL1 interaction plays an important role in cardiac APN resistance to MI/R injury in diabetic mice.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2023 ","pages":"7441367"},"PeriodicalIF":4.3,"publicationDate":"2023-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9970717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10812313","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":"Nucleus Pulposus Cells Induce M2 Polarization of RAW264.7 via CX3CL1/CX3CR1 Pathway and M2 Macrophages Promote Proliferation and Anabolism of Nucleus Pulposus Cells.","authors":"Xiao-Tao Wu, Bo-Wen Wan, Xin-Min Feng, Yu-Ping Tao, Yong-Xiang Wang, Hui-Hui Sun","doi":"10.1155/2023/6400162","DOIUrl":"10.1155/2023/6400162","url":null,"abstract":"<p><strong>Background: </strong>The mechanisms underlying M2 macrophage polarization induced by nucleus pulposus (NP) cells are unclear. The effects that M2-polarized macrophages have on NP cells are also controversial.</p><p><strong>Methods: </strong>Transcriptome sequencing was performed to detect the gene change profiles between NP cells from ruptured intervertebral disc (IVD) and normal IVD. The main difference on biological activities between the two cell groups were analyzed by GO analysis and KEGG analysis. Virus transduction, flow cytometry, immunofluorescence, RT-PCR, western blot, CCK-8, TUNEL staining, and AO/EB staining were performed to explore the interactions between NP cells and RAW264.7 macrophages. Statistics were performed using SPSS26.</p><p><strong>Results: </strong>801 upregulated and 276 downregulated genes were identified in NP cells from ruptured IVD in mouse models. According to GO and KEGG analysis, we found that the differentially expressed genes (DEG) were dominantly enriched in inflammatory response, extracellular matrix degradation, blood vessel morphogenesis, immune effector process, ossification, chemokine signaling pathway, macrophage activation, etc. CX3CL1 was one of the top 20% DEG, and we confirmed that both NP tissue and cells expressed remarkably higher level of CX3CL1 in mouse models (<i>p</i> < 0.001<sup>∗</sup>). Besides, we further revealed that both the recombinant CX3CL1 and NP cells remarkably induced M2 polarization of RAW264.7 (<i>p</i> < 0.001<sup>∗</sup>), respectively, while this effect was significantly reversed by si-CX3CL1 or JMS-17-2 (<i>p</i> < 0.001<sup>∗</sup>). Furthermore, we found that M2 macrophages significantly decreased the apoptosis rate (<i>p</i> < 0.001<sup>∗</sup>) and the catabolic gene levels (<i>p</i> < 0.001<sup>∗</sup>) of NP cells, while increased the viability, proliferation as well as the anabolic gene levels of NP cells (<i>p</i> < 0.01<sup>∗</sup>).</p><p><strong>Conclusions: </strong>Via regulating CX3CL1/CX3CR1 pathway, NP cells can induce the M2 macrophage polarization. M2 polarized macrophages can further promote NP cell viability, proliferation, and anabolism, while inhibit NP cell apoptosis and catabolism.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2023 ","pages":"6400162"},"PeriodicalIF":4.3,"publicationDate":"2023-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9934420","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}
Stem Cells InternationalPub Date : 2023-02-17eCollection Date: 2023-01-01DOI: 10.1155/2023/9821500
Fengguang Li, Yan Xu, Xinghua Wang, Xuan Cai, Wanli Li, Wei Cheng, Xing Li, Gangli Yan
{"title":"Block Copolymer Nanomicelle-Encapsulated Curcumin Attenuates Cerebral Ischemia Injury and Affects Stem Cell Marker Expression by Inhibiting lncRNA GAS5.","authors":"Fengguang Li, Yan Xu, Xinghua Wang, Xuan Cai, Wanli Li, Wei Cheng, Xing Li, Gangli Yan","doi":"10.1155/2023/9821500","DOIUrl":"10.1155/2023/9821500","url":null,"abstract":"<p><p>Stroke has become the most common cause of death among residents in China, among which ischemic stroke accounts for the vast majority reaching 70% to 80%. It is of great importance to actively investigate the protective mechanism of cerebral ischemia injury after IS (ischemic stroke). We constructed cerebral ischemia injury models <i>in vivo</i> MACO rat and <i>in vitro</i> (oxygen-glucose deprivation cell model) and set up different interference groups. RT-PCR (reverse transcription PCR) was conducted to detect the expression of lncRNA in neuronal cells, brain tissue, and plasma of different groups, and ELISA (enzyme-linked immunosorbent assay) and western blot were used to detect the expression of the protein in neuronal cells, brain tissue, and plasma of different groups. Cell activity was detected by the CCK-8 assay, while cell apoptosis was examined by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay. In the rats' neuronal cells and brain tissue, curcumin can inhibit the expression of lncRNA GAS5 (long noncoding RNA growth arrest-specific 5). In oxygen-glucose-deprived neuronal cells <i>in vitro</i>, curcumin and low-expressed lncRNA GAS5 can enhance cell activity and decline cell apoptosis, but the addition of curcumin and overexpressed lncRNA GAS5 can make this phenomenon disappear. In neuronal cells, plasma, and brain tissue, curcumin and the low-expressed lncRNA GAS5 can inhibit the expression of IL-1<i>β</i> (interleukin 1 beta), TNF-<i>α</i> (tumor necrosis factor alpha), IL-6 (interleukin 6), Sox2 (SRY-box transcription factor 2), Nanog, and Oct4 (octamer-binding transcription factor 4). However, overexpressed lncRNA GAS5 and curcumin made the inhibitory effect disappear. In conclusion, this study demonstrated that curcumin could inhibit the expression of lncRNA GAS5, thereby inhibiting the expression of inflammation-related factors IL-1<i>β</i>, TNF-<i>α</i>, and IL-6, and ultimately achieve the purpose of attenuating cerebral ischemic cell damage. However, curcumin and lncRNA GAS5 may not alleviate cerebral ischemic cell damage by affecting stem cell differentiation.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2023 ","pages":"9821500"},"PeriodicalIF":4.3,"publicationDate":"2023-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9957624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10851285","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}