World journal of stem cells最新文献

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Outcomes of combined mitochondria and mesenchymal stem cells-derived exosome therapy in rat acute respiratory distress syndrome and sepsis. 线粒体和间充质干细胞衍生外泌体联合疗法对大鼠急性呼吸窘迫综合征和败血症的疗效。
IF 3.6 3区 医学
World journal of stem cells Pub Date : 2024-06-26 DOI: 10.4252/wjsc.v16.i6.690
Kun-Chen Lin, Wen-Feng Fang, Jui-Ning Yeh, John Y Chiang, Hsin-Ju Chiang, Pei-Lin Shao, Pei-Hsun Sung, Hon-Kan Yip
{"title":"Outcomes of combined mitochondria and mesenchymal stem cells-derived exosome therapy in rat acute respiratory distress syndrome and sepsis.","authors":"Kun-Chen Lin, Wen-Feng Fang, Jui-Ning Yeh, John Y Chiang, Hsin-Ju Chiang, Pei-Lin Shao, Pei-Hsun Sung, Hon-Kan Yip","doi":"10.4252/wjsc.v16.i6.690","DOIUrl":"10.4252/wjsc.v16.i6.690","url":null,"abstract":"<p><strong>Background: </strong>The treatment of acute respiratory distress syndrome (ARDS) complicated by sepsis syndrome (SS) remains challenging.</p><p><strong>Aim: </strong>To investigate whether combined adipose-derived mesenchymal-stem-cells (ADMSCs)-derived exosome (EX<sup>AD</sup>) and exogenous mitochondria (mito<sup>Ex</sup>) protect the lung from ARDS complicated by SS.</p><p><strong>Methods: </strong><i>In vitro</i> study, including L2 cells treated with lipopolysaccharide (LPS) and <i>in vivo</i> study including male-adult-SD rats categorized into groups 1 (sham-operated-control), 2 (ARDS-SS), 3 (ARDS-SS + EX<sup>AD</sup>), 4 (ARDS-SS + mito<sup>Ex</sup>), and 5 (ARDS-SS + EX<sup>AD</sup> + mito<sup>Ex</sup>), were included in the present study.</p><p><strong>Results: </strong><i>In vitro</i> study showed an abundance of mito<sup>Ex</sup> found in recipient-L2 cells, resulting in significantly higher mitochondrial-cytochrome-C, adenosine triphosphate and relative mitochondrial DNA levels (<i>P</i> < 0.001). The protein levels of inflammation [interleukin (IL)-1β/tumor necrosis factor (TNF)-α/nuclear factor-κB/toll-like receptor (TLR)-4/matrix-metalloproteinase (MMP)-9/oxidative-stress (NOX-1/NOX-2)/apoptosis (cleaved-caspase3/cleaved-poly (ADP-ribose) polymerase)] were significantly attenuated in lipopolysaccharide (LPS)-treated L2 cells with EX<sup>AD</sup> treatment than without EX<sup>AD</sup> treatment, whereas the protein expressions of cellular junctions [occluding/β-catenin/zonula occludens (ZO)-1/E-cadherin] exhibited an opposite pattern of inflammation (all <i>P</i> < 0.001). Animals were euthanized by 72 h post-48 h-ARDS induction, and lung tissues were harvested. By 72 h, flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that the levels of inflammatory cells (Ly6G+/CD14+/CD68+/CD11<sup>b/c</sup>+/myeloperoxidase+) and albumin were lowest in group 1, highest in group 2, and significantly higher in groups 3 and 4 than in group 5 (all <i>P</i> < 0.0001), whereas arterial oxygen-saturation (SaO<sub>2</sub>%) displayed an opposite pattern of albumin among the groups. Histopathological findings of lung injury/fibrosis area and inflammatory/DNA-damaged markers (CD68+/γ-H2AX) displayed an identical pattern of SaO<sub>2</sub>% among the groups (all <i>P</i> < 0.0001). The protein expressions of inflammatory (TLR-4/MMP-9/IL-1β/TNF-α)/oxidative stress (NOX-1/NOX-2/p22phox/oxidized protein)/mitochondrial-damaged (cytosolic-cytochrome-C/dynamin-related protein 1)/autophagic (beclin-1/Atg-5/ratio of LC3B-II/LC3B-I) biomarkers exhibited a similar manner, whereas antioxidants [nuclear respiratory factor (Nrf)-1/Nrf-2]/cellular junctions (ZO-1/E-cadherin)/mitochondrial electron transport chain (complex I-V) exhibited an opposite manner of albumin among the groups (all <i>P</i> < 0.0001).</p><p><strong>Conclusion: </strong>Combined EX<sup>AD</sup>-mito<sup>Ex</sup> therapy was better than merely one for protecting the lu","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 6","pages":"690-707"},"PeriodicalIF":3.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471113","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}
引用次数: 0
Priming mesenchymal stem cells to develop "super stem cells". 引导间充质干细胞发展 "超级干细胞"。
IF 3.6 3区 医学
World journal of stem cells Pub Date : 2024-06-26 DOI: 10.4252/wjsc.v16.i6.623
Khawaja Husnain Haider
{"title":"Priming mesenchymal stem cells to develop \"super stem cells\".","authors":"Khawaja Husnain Haider","doi":"10.4252/wjsc.v16.i6.623","DOIUrl":"10.4252/wjsc.v16.i6.623","url":null,"abstract":"<p><p>The stem cell pre-treatment approaches at cellular and sub-cellular levels encompass physical manipulation of stem cells to growth factor treatment, genetic manipulation, and chemical and pharmacological treatment, each strategy having advantages and limitations. Most of these pre-treatment protocols are non-combinative. This editorial is a continuum of Li <i>et al</i>'s published article and Wan <i>et al</i>'s editorial focusing on the significance of pre-treatment strategies to enhance their stemness, immunoregulatory, and immunosuppressive properties. They have elaborated on the intricacies of the combinative pre-treatment protocol using pro-inflammatory cytokines and hypoxia. Applying a well-defined multi-pronged combinatorial strategy of mesenchymal stem cells (MSCs), pre-treatment based on the mechanistic understanding is expected to develop \"Super MSCs\", which will create a transformative shift in MSC-based therapies in clinical settings, potentially revolutionizing the field. Once optimized, the standardized protocols may be used with slight modifications to pre-treat different stem cells to develop \"super stem cells\" with augmented stemness, functionality, and reparability for diverse clinical applications with better outcomes.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 6","pages":"623-640"},"PeriodicalIF":3.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471114","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}
引用次数: 0
RPLP0/TBP are the most stable reference genes for human dental pulp stem cells under osteogenic differentiation. RPLP0/TBP是人牙髓干细胞成骨分化过程中最稳定的参考基因。
IF 3.6 3区 医学
World journal of stem cells Pub Date : 2024-06-26 DOI: 10.4252/wjsc.v16.i6.656
Daniel B Ferreira, Leticia M Gasparoni, Cristiane F Bronzeri, Katiucia B S Paiva
{"title":"RPLP0/TBP are the most stable reference genes for human dental pulp stem cells under osteogenic differentiation.","authors":"Daniel B Ferreira, Leticia M Gasparoni, Cristiane F Bronzeri, Katiucia B S Paiva","doi":"10.4252/wjsc.v16.i6.656","DOIUrl":"10.4252/wjsc.v16.i6.656","url":null,"abstract":"<p><strong>Background: </strong>Validation of the reference gene (RG) stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction (RT-qPCR) data normalisation. Commonly, in an unreliable way, several studies use genes involved in essential cellular functions [glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 18S rRNA, and β-actin] without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such genes. Furthermore, such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recommend two or more genes. It impacts the credibility of these studies and causes distortions in the gene expression findings. For tissue engineering, the accuracy of gene expression drives the best experimental or therapeutical approaches.</p><p><strong>Aim: </strong>To verify the most stable RG during osteogenic differentiation of human dental pulp stem cells (DPSCs) by RT-qPCR.</p><p><strong>Methods: </strong>We cultivated DPSCs under two conditions: Undifferentiated and osteogenic differentiation, both for 35 d. We evaluated the gene expression of 10 candidates for RGs [ribosomal protein, large, P0 (<i>RPLP0</i>), TATA-binding protein (<i>TBP</i>), <i>GAPDH</i>, actin beta (<i>ACTB</i>), tubulin (<i>TUB</i>), aminolevulinic acid synthase 1 (<i>ALAS1</i>), tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta (<i>YWHAZ</i>), eukaryotic translational elongation factor 1 alpha (<i>EF1a</i>), succinate dehydrogenase complex, subunit A, flavoprotein (<i>SDHA</i>), and beta-2-microglobulin (<i>B2M</i>)] every 7 d (1, 7, 14, 21, 28, and 35 d) by RT-qPCR. The data were analysed by the four main algorithms, ΔCt method, geNorm, NormFinder, and BestKeeper and ranked by the RefFinder method. We subdivided the samples into eight subgroups.</p><p><strong>Results: </strong>All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder algorithm. The final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable RGs. Either the ΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable genes. However, geNorm analysis showed RPLP0/EF1α in the first place. These algorithms' two least stable RGs were B2M/GAPDH. For BestKeeper, ALAS1 was ranked as the most stable RG, and SDHA as the least stable RG. The pair RPLP0/TBP was detected in most subgroups as the most stable RGs, following the RefFinfer ranking.</p><p><strong>Conclusion: </strong>For the first time, we show that RPLP0/TBP are the most stable RGs, whereas TUB/B2M are unstable RGs for long-term osteogenic differentiation of human DPSCs in traditional monolayers.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 6","pages":"656-669"},"PeriodicalIF":3.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471115","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}
引用次数: 0
Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments. 胶质瘤干细胞在促进肿瘤化疗和放射抗药性方面的作用:潜在靶向治疗的系统回顾。
IF 4.1 3区 医学
World journal of stem cells Pub Date : 2024-05-26 DOI: 10.4252/wjsc.v16.i5.604
Edoardo Agosti, Marco Zeppieri, Mattia Ghidoni, Tamara Ius, Alessandro Tel, Marco Maria Fontanella, Pier Paolo Panciani
{"title":"Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments.","authors":"Edoardo Agosti, Marco Zeppieri, Mattia Ghidoni, Tamara Ius, Alessandro Tel, Marco Maria Fontanella, Pier Paolo Panciani","doi":"10.4252/wjsc.v16.i5.604","DOIUrl":"10.4252/wjsc.v16.i5.604","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy. Glioma stem cells (GSCs), a subset within tumors, contribute to resistance, tumor heterogeneity, and plasticity. Recent studies reveal GSCs' role in therapeutic resistance, driven by DNA repair mechanisms and dynamic transitions between cellular states. Resistance mechanisms can involve different cellular pathways, most of which have been recently reported in the literature. Despite progress, targeted therapeutic approaches lack consensus due to GSCs' high plasticity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;To analyze targeted therapies against GSC-mediated resistance to radio- and chemotherapy in gliomas, focusing on underlying mechanisms.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to September 30, 2023. The search strategy utilized relevant Medical Subject Heading terms and keywords related to including \"glioma stem cells\", \"radiotherapy\", \"chemotherapy\", \"resistance\", and \"targeted therapies\". Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated resistance to radiotherapy resistance (RTR).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In a comprehensive review of 66 studies on stem cell therapies for SCI, 452 papers were initially identified, with 203 chosen for full-text analysis. Among them, 201 were deemed eligible after excluding 168 for various reasons. The temporal breakdown of studies illustrates this trend: 2005-2010 (33.3%), 2011-2015 (36.4%), and 2016-2022 (30.3%). Key GSC models, particularly U87 (33.3%), U251 (15.2%), and T98G (15.2%), emerge as significant in research, reflecting their representativeness of glioma characteristics. Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) (27.3%) and Notch (12.1%) pathways, suggesting their crucial roles in resistance development. Targeted molecules with mTOR (18.2%), CHK1/2 (15.2%), and ATP binding cassette G2 (12.1%) as frequent targets underscore their importance in overcoming GSC-mediated resistance. Various therapeutic agents, notably RNA inhibitor/short hairpin RNA (27.3%), inhibitors (&lt;i&gt;e.g.,&lt;/i&gt; LY294002, NVP-BEZ235) (24.2%), and monoclonal antibodies (&lt;i&gt;e.g.,&lt;/i&gt; cetuximab) (9.1%), demonstrate versatility in targeted therapies. among 20 studies (60.6%), the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance (51.5%), followed by reductions in carmustine resistance (9.1%) and doxorubicin resistance (3.0%), while resistance to RTR is reduced in 42.4% of studies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;GSCs play a complex role in mediating radioresistance and chemoresistance, emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population an","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 5","pages":"604-614"},"PeriodicalIF":4.1,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11135247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180881","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}
引用次数: 0
Advances in the differentiation of pluripotent stem cells into vascular cells. 将多能干细胞分化为血管细胞的进展。
IF 4.1 3区 医学
World journal of stem cells Pub Date : 2024-02-26 DOI: 10.4252/wjsc.v16.i2.137
Yi-Chang Jiao, Ying-Xin Wang, Wen-Zhu Liu, Jing-Wen Xu, Yu-Ying Zhao, Chuan-Zhu Yan, Fu-Chen Liu
{"title":"Advances in the differentiation of pluripotent stem cells into vascular cells.","authors":"Yi-Chang Jiao, Ying-Xin Wang, Wen-Zhu Liu, Jing-Wen Xu, Yu-Ying Zhao, Chuan-Zhu Yan, Fu-Chen Liu","doi":"10.4252/wjsc.v16.i2.137","DOIUrl":"10.4252/wjsc.v16.i2.137","url":null,"abstract":"<p><p>Blood vessels constitute a closed pipe system distributed throughout the body, transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys. Changes in blood vessels are related to many disorders like stroke, myocardial infarction, aneurysm, and diabetes, which are important causes of death worldwide. Translational research for new approaches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems. Although mice or rats have been widely used, applying data from animal studies to human-specific vascular physiology and pathology is difficult. The rise of induced pluripotent stem cells (iPSCs) provides a reliable <i>in vitro</i> resource for disease modeling, regenerative medicine, and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells. This review summarizes the latest progress from the establishment of iPSCs, the strategies for differentiating iPSCs into vascular cells, and the <i>in vivo</i> transplantation of these vascular derivatives. It also introduces the application of these technologies in disease modeling, drug screening, and regenerative medicine. Additionally, the application of high-tech tools, such as omics analysis and high-throughput sequencing, in this field is reviewed.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 2","pages":"137-150"},"PeriodicalIF":4.1,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060602","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}
引用次数: 0
Cellular preconditioning and mesenchymal stem cell ferroptosis. 细胞预处理和间充质干细胞铁突变。
IF 4.1 3区 医学
World journal of stem cells Pub Date : 2024-02-26 DOI: 10.4252/wjsc.v16.i2.64
Doaa Hussein Zineldeen, Mazhar Mushtaq, Khawaja Husnain Haider
{"title":"Cellular preconditioning and mesenchymal stem cell ferroptosis.","authors":"Doaa Hussein Zineldeen, Mazhar Mushtaq, Khawaja Husnain Haider","doi":"10.4252/wjsc.v16.i2.64","DOIUrl":"10.4252/wjsc.v16.i2.64","url":null,"abstract":"<p><p>In this editorial, we comment on the article published in the recent issue of the <i>World Journal of Stem Cells</i>. They focus on stem cell preconditioning to prevent ferroptosis by modulating the cystathionine γ-lyase/hydrogen sulfide (H<sub>2</sub>S) pathway as a novel approach to treat vascular disorders, particularly pulmonary hypertension. Preconditioned stem cells are gaining popularity in regenerative medicine due to their unique ability to survive by resisting the harsh, unfavorable microenvironment of the injured tissue. They also secrete various paracrine factors against apoptosis, necrosis, and ferroptosis to enhance cell survival. Ferroptosis, a regulated form of cell death characterized by iron accumulation and oxidative stress, has been implicated in various pathologies encompassing degenerative disorders to cancer. The lipid peroxidation cascade initiates and sustains ferroptosis, generating many reactive oxygen species that attack and damage multiple cellular structures. Understanding these intertwined mechanisms provides significant insights into developing therapeutic modalities for ferroptosis-related diseases. This editorial primarily discusses stem cell preconditioning in modulating ferroptosis, focusing on the cystathionase gamma/H<sub>2</sub>S ferroptosis pathway. Ferroptosis presents a significant challenge in mesenchymal stem cell (MSC)-based therapies; hence, the emerging role of H<sub>2</sub>S/cystathionase gamma/H<sub>2</sub>S signaling in abrogating ferroptosis provides a novel option for therapeutic intervention. Further research into understanding the precise mechanisms of H<sub>2</sub>S-mediated cytoprotection against ferroptosis is warranted to enhance the therapeutic potential of MSCs in clinical settings, particularly vascular disorders.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 2","pages":"64-69"},"PeriodicalIF":4.1,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060603","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}
引用次数: 0
VX-509 attenuates the stemness characteristics of colorectal cancer stem-like cells by regulating the epithelial-mesenchymal transition through Nodal/Smad2/3 signaling. VX-509通过Nodal/Smad2/3信号调节上皮-间质转化,从而减轻结直肠癌干样细胞的干性特征。
IF 4.1 3区 医学
World journal of stem cells Pub Date : 2024-02-26 DOI: 10.4252/wjsc.v16.i2.207
Yun Yuan, Xu-Fan Zhang, Yu-Chen Li, Hong-Qing Chen, Tian Wen, Jia-Lian Zheng, Zi-Yi Zhao, Qiong-Ying Hu
{"title":"VX-509 attenuates the stemness characteristics of colorectal cancer stem-like cells by regulating the epithelial-mesenchymal transition through Nodal/Smad2/3 signaling.","authors":"Yun Yuan, Xu-Fan Zhang, Yu-Chen Li, Hong-Qing Chen, Tian Wen, Jia-Lian Zheng, Zi-Yi Zhao, Qiong-Ying Hu","doi":"10.4252/wjsc.v16.i2.207","DOIUrl":"10.4252/wjsc.v16.i2.207","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer stem cells (CCSCs) are heterogeneous cells that can self-renew and undergo multidirectional differentiation in colorectal cancer (CRC) patients. CCSCs are generally accepted to be important sources of CRC and are responsible for the progression, metastasis, and therapeutic resistance of CRC. Therefore, targeting this specific subpopulation has been recognized as a promising strategy for overcoming CRC.</p><p><strong>Aim: </strong>To investigate the effect of VX-509 on CCSCs and elucidate the underlying mechanism.</p><p><strong>Methods: </strong>CCSCs were enriched from CRC cell lines by in conditioned serum-free medium. Western blot, Aldefluor, transwell and tumorigenesis assays were performed to verify the phenotypic characteristics of the CCSCs. The anticancer efficacy of VX-509 was assessed in HCT116 CCSCs and HT29 CCSCs by performing cell viability analysis, colony formation, sphere formation, flow cytometry, and western blotting assessments <i>in vitro</i> and tumor growth, immunohistochemistry and immunofluorescence assessments <i>in vivo</i>.</p><p><strong>Results: </strong>Compared with parental cells, sphere cells derived from HCT116 and HT29 cells presented increased expression of stem cell transcription factors and stem cell markers and were more potent at promoting migration and tumorigenesis, demonstrating that the CRC sphere cells displayed CSC features. VX-509 inhibited the tumor malignant biological behavior of CRC-stem-like cells, as indicated by their proliferation, migration and clonality <i>in vitro</i>, and suppressed the tumor of CCSC-derived xenograft tumors <i>in vivo</i>. Besides, VX-509 suppressed the CSC characteristics of CRC-stem-like cells and inhibited the progression of epithelial-mesenchymal transition (EMT) signaling <i>in vitro</i>. Nodal was identified as the regulatory factor of VX-509 on CRC stem-like cells through analyses of differentially expressed genes and CSC-related database information. VX-509 markedly downregulated the expression of Nodal and its downstream phosphorylated Smad2/3 to inhibit EMT progression. Moreover, VX-509 reversed the dedifferentiation of CCSCs and inhibited the progression of EMT induced by Nodal overexpression.</p><p><strong>Conclusion: </strong>VX-509 prevents the EMT process in CCSCs by inhibiting the transcription and protein expression of Nodal, and inhibits the dedifferentiated self-renewal of CCSCs.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 2","pages":"207-227"},"PeriodicalIF":4.1,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060650","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}
引用次数: 0
High quality repair of osteochondral defects in rats using the extracellular matrix of antler stem cells. 利用鹿茸干细胞细胞外基质高质量修复大鼠骨软骨缺损。
IF 4.1 3区 医学
World journal of stem cells Pub Date : 2024-02-26 DOI: 10.4252/wjsc.v16.i2.176
Yu-Su Wang, Wen-Hui Chu, Jing-Jie Zhai, Wen-Ying Wang, Zhong-Mei He, Quan-Min Zhao, Chun-Yi Li
{"title":"High quality repair of osteochondral defects in rats using the extracellular matrix of antler stem cells.","authors":"Yu-Su Wang, Wen-Hui Chu, Jing-Jie Zhai, Wen-Ying Wang, Zhong-Mei He, Quan-Min Zhao, Chun-Yi Li","doi":"10.4252/wjsc.v16.i2.176","DOIUrl":"10.4252/wjsc.v16.i2.176","url":null,"abstract":"<p><strong>Background: </strong>Cartilage defects are some of the most common causes of arthritis. Cartilage lesions caused by inflammation, trauma or degenerative disease normally result in osteochondral defects. Previous studies have shown that decellularized extracellular matrix (ECM) derived from autologous, allogenic, or xenogeneic mesenchymal stromal cells (MSCs) can effectively restore osteochondral integrity.</p><p><strong>Aim: </strong>To determine whether the decellularized ECM of antler reserve mesenchymal cells (RMCs), a xenogeneic material from antler stem cells, is superior to the currently available treatments for osteochondral defects.</p><p><strong>Methods: </strong>We isolated the RMCs from a 60-d-old sika deer antler and cultured them <i>in vitro</i> to 70% confluence; 50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition. Decellularized sheets of adipocyte-derived MSCs (aMSCs) and antlerogenic periosteal cells (another type of antler stem cells) were used as the controls. Three weeks after ascorbic acid stimulation, the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints.</p><p><strong>Results: </strong>The defects were successfully repaired by applying the ECM-sheets. The highest quality of repair was achieved in the RMC-ECM group both <i>in vitro</i> (including cell attachment and proliferation), and <i>in vivo</i> (including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues). Notably, the antler-stem-cell-derived ECM (xenogeneic) performed better than the aMSC-ECM (allogenic), while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells.</p><p><strong>Conclusion: </strong>Decellularized xenogeneic ECM derived from the antler stem cell, particularly the active form (RMC-ECM), can achieve high quality repair/reconstruction of osteochondral defects, suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 2","pages":"176-190"},"PeriodicalIF":4.1,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060606","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}
引用次数: 0
Effects of different concentrations of nicotinamide on hematopoietic stem cells cultured in vitro. 不同浓度的烟酰胺对体外培养造血干细胞的影响。
IF 4.1 3区 医学
World journal of stem cells Pub Date : 2024-02-26 DOI: 10.4252/wjsc.v16.i2.163
Yan Ren, Yan-Ni Cui, Hong-Wei Wang
{"title":"Effects of different concentrations of nicotinamide on hematopoietic stem cells cultured <i>in vitro</i>.","authors":"Yan Ren, Yan-Ni Cui, Hong-Wei Wang","doi":"10.4252/wjsc.v16.i2.163","DOIUrl":"10.4252/wjsc.v16.i2.163","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;&lt;i&gt;In vitro&lt;/i&gt; expansion to increase numbers of hematopoietic stem cells (HSCs) in cord blood could improve clinical efficacy of this vital resource. Nicotinamide (NAM) can promote HSC expansion &lt;i&gt;ex vivo&lt;/i&gt;, but its effect on hematopoietic stem and progenitor cells (HSPCs, CD34&lt;sup&gt;+&lt;/sup&gt;CD38) and functional subtypes of HSCs - short-term repopulating HSCs (ST-HSCs, CD34&lt;sup&gt;+&lt;/sup&gt;CD38CD45RACD49f&lt;sup&gt;+&lt;/sup&gt;) and long-term repopulating HSCs (LT-HSCs, CD34&lt;sup&gt;+&lt;/sup&gt;CD38CD45RACD49f&lt;sup&gt;+&lt;/sup&gt;CD90&lt;sup&gt;+&lt;/sup&gt;) is not yet known. As a sirtuin 1 (SIRT1) inhibitor, NAM participates in regulating cell adhesion, polarity, migration, proliferation, and differentiation. However, SIRT1 exhibits dual effects by promoting or inhibiting differentiation in different tissues or cells. We propose that the concentration of NAM may influence proliferation, differentiation, and SIRT1 signaling of HSCs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;To evaluate the effects and underlying mechanisms of action of different concentrations of NAM on HSC proliferation and differentiation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;CD34&lt;sup&gt;+&lt;/sup&gt; cells were purified from umbilical cord blood using MacsCD34 beads, and cultured for 10-12 d in a serum-free medium supplemented with cytokines, with different concentrations of NAM added according to experimental requirements. Flow cytometry was used to detect phenotype, cell cycle distribution, and apoptosis of the cultured cells. Real-time polymerase chain reaction was used to detect the transcription levels of target genes encoding stemness-related factors, chemokines, components of hypoxia pathways, and antioxidant enzymes. Dichloro-dihydro-fluorescein diacetate probes were used to evaluate intracellular production of reactive oxygen species (ROS). Determination of the effect of different culture conditions on the balance of cytokine by cytometric bead array.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compared with the control group, the proportion and expansion folds of HSPCs (CD34&lt;sup&gt;+&lt;/sup&gt;CD38) incubated with 5 mmol/L or 10 mmol/L NAM were significantly increased (all &lt;i&gt;P&lt;/i&gt; &lt; 0.05). The ST-HSCs ratio and fold expansion of the 5 mmol/L NAM group were significantly higher than those of the control and 10 mmol/L NAM groups (all &lt;i&gt;P&lt;/i&gt; &lt; 0.001), whereas the LT-HSCs ratio and fold expansion of the 10 mmol/L NAM group were significantly higher than those of the other two groups (all &lt;i&gt;P&lt;/i&gt; &lt; 0.05). When the NAM concentration was &gt; 10 mmol/L, cell viability significantly decreased. In addition, compared with the 5 mmol/L NAM group, the proportion of apoptotic cells in the 10 mmol/L NAM group increased and the proportion of cells in S and G2 phase decreased. Compared with the 5 mmol/L NAM group, the HSCs incubated with 10 mmol/L NAM exhibited significantly inhibited SIRT1 expression, increased intracellular ROS content, and downregulated expression of genes encoding antioxidant enzymes (superoxide dismutase 1, peroxiredox","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 2","pages":"163-175"},"PeriodicalIF":4.1,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060604","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}
引用次数: 0
Human pluripotent stem cell-derived kidney organoids: Current progress and challenges. 人类多能干细胞衍生肾脏器官组织:当前的进展与挑战。
IF 4.1 3区 医学
World journal of stem cells Pub Date : 2024-02-26 DOI: 10.4252/wjsc.v16.i2.114
Hong-Yan Long, Zu-Ping Qian, Qin Lan, Yong-Jie Xu, Jing-Jing Da, Fu-Xun Yu, Yan Zha
{"title":"Human pluripotent stem cell-derived kidney organoids: Current progress and challenges.","authors":"Hong-Yan Long, Zu-Ping Qian, Qin Lan, Yong-Jie Xu, Jing-Jing Da, Fu-Xun Yu, Yan Zha","doi":"10.4252/wjsc.v16.i2.114","DOIUrl":"10.4252/wjsc.v16.i2.114","url":null,"abstract":"<p><p>Human pluripotent stem cell (hPSC)-derived kidney organoids share similarities with the fetal kidney. However, the current hPSC-derived kidney organoids have some limitations, including the inability to perform nephrogenesis and lack of a corticomedullary definition, uniform vascular system, and coordinated exit pathway for urinary filtrate. Therefore, further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development, regeneration, disease modeling, and drug screening. In this review, we discussed recent advances in the generation of hPSC-derived kidney organoids, how these organoids contribute to the understanding of human kidney development and research in disease modeling. Additionally, the limitations, future research focus, and applications of hPSC-derived kidney organoids were highlighted.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"16 2","pages":"114-125"},"PeriodicalIF":4.1,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060644","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}
引用次数: 0
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