Xianyun Qin, Lu Zhang, Jilan Liu, Yan Lu, Fuyao Zhou, Feng Jin
{"title":"Shikonin Induces Glioma Necroptosis, Stemness Decline, and Impedes (Immuno)Proteasome Activity","authors":"Xianyun Qin, Lu Zhang, Jilan Liu, Yan Lu, Fuyao Zhou, Feng Jin","doi":"10.1155/2024/1348269","DOIUrl":"https://doi.org/10.1155/2024/1348269","url":null,"abstract":"Gliomas, the most prevalent primary intracranial tumors, exhibit notable features such as heightened malignancy, rapid recurrence, and elevated mortality rates. Presently, standard therapeutic approaches yield limited curative outcomes. Shikonin, an extract derived from traditional Chinese medicine, demonstrates notable bioactivity against various tumors, including gliomas. This study elucidates Shikonin’s capacity to effectively induce necroptosis in glioma cells, concurrently mitigating glioma stemness, as evidenced by diminished levels of stem cell markers, namely SOX2, CD44, CHI3L1, and CD24. Our findings indicate that Shikonin-induced programed necrosis leads to a downregulation of proteasome activity and a decrease in the expression of immune proteasome subunits PSMB8/9/10 and PSME1/2/3, contributing to the attenuation of stemness in gliomas. This study comprehensively investigates the interplay between (immuno)proteasome dynamics, Shikonin-mediated necroptosis, and the consequential reduction in glioma stemness, both in vitro and in vivo. The discussion extends to the potential of Shikonin as a promising therapeutic agent in the management of gliomas, offering a novel avenue for drug development in this challenging clinical context.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"16 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140128955","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}
Xiaru Zhang, Ying Zheng, Gang Wang, Yuanlin Liu, Yang Wang, Xueyi Jiang, Yueqing Liang, Xinfeng Zhao, Ping Li, Yi Zhang
{"title":"Stimulated Human Umbilical Cord Mesenchymal Stem Cells Enhance the Osteogenesis and Cranial Bone Regeneration through IL-32 Mediated P38 Signaling Pathway","authors":"Xiaru Zhang, Ying Zheng, Gang Wang, Yuanlin Liu, Yang Wang, Xueyi Jiang, Yueqing Liang, Xinfeng Zhao, Ping Li, Yi Zhang","doi":"10.1155/2024/6693292","DOIUrl":"https://doi.org/10.1155/2024/6693292","url":null,"abstract":"<i>Objective</i>. Our previous study found that it could significantly increase the expression of IL32 after stimulating the human umbilical cord mesenchymal stem cells (S-HuMSCs). However, its role on the osteogenesis and cranial bone regeneration is still largely unknown. Here, we investigated the possible mechanism of this effect. <i>Material and Methods</i>. A series of experiments, including single-cell sequencing, flow cytometry, quantitative real-time polymerase chain reaction, and western blotting, were carried out to evaluate the characteristic and adipogenic–osteogenic differentiation potential of IL-32 overexpression HuMSCs (IL-32<sup>high</sup>HuMSCs) through mediating the P38 signaling pathway. Moreover, a rat skull bone defect model was established and treated by directly injecting the IL-32<sup>high</sup>HuMSCs to conduct its role on the cranial bone regeneration. <i>Results</i>. In total, it found that compared to HuMSCs, IL32 was significantly increased and promoted the osteogenic differentiation (lower expressions of PPAR<i>γ</i>, Adiponectin, and C/EBP<i>α</i>, and increased expressions of RUNX2, ALP, BMP2, OPN, SP7, OCN, and DLX5) in the S-HuMSCs (<span><svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 19.289 9.2729\" width=\"19.289pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"></path></g></svg><span></span><span><svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"22.8711838 -8.6359 21.918 9.2729\" width=\"21.918pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,32.125,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,38.365,0)\"></path></g></svg>).</span></span> Meanwhile, the enhanced osteogenic differentiation of HuMSCs was recovered by IL-32 overexpression (IL-32<sup>high</sup>HuMSCs) through activating the P38 signaling pathway, like as the S-HuMSCs (<span><svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.6359 19.289 9.2729\" width=\"19.289pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"><use xlink:href=\"#g113-81\"></use></g><g transform=\"matrix(.013,0,0,-0.013,11.658,0)\"><use xlink:href=\"#g117-91\"></use></g></svg><span></span><span><svg height=\"9.2729pt\" style=\"vertical-align:-0.6370001pt\" version=\"1.1\" viewbox=\"22.8711838 -8.6359 21.918 9.2729\" width=\"21.918pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,22.921,0)\"><use xlink:href=\"#g113-49\"></use></g><g transform=\"matrix(.013,0,0,-0.013,29.161,0)\"><use xlink:href=","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"116 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140114918","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":"Periostin Is a Candidate Regulator of the Host Microenvironment in Regeneration of Pulp and Dentin Complex and Periodontal Ligament in Transplantation with Stem Cell-Conditioned Medium","authors":"Shintarou Sakatoku, Yuki Hayashi, Taku Futenma, Yoshihiko Sugita, Ryo Ishizaka, Hiroyuki Nawa, Koichiro Iohara","doi":"10.1155/2024/7685280","DOIUrl":"https://doi.org/10.1155/2024/7685280","url":null,"abstract":"<i>Purpose</i>. The microenvironment is required for tissues to maintain their properties <i>in vivo</i>. This microenvironment encompasses the types and three-dimensional arrangement of cells forming the tissues, and their interactions with neighboring cells and extracellular matrices, as represented by the stem cell niche. Tissue regeneration depends not on the original tissue source of the transplanted cells, but on the microenvironment in which they are transplanted. We have previously reported pulp regeneration in a heterotopic root graft model by transplantation of conditioned medium alone, which suggests that host-derived cells expressing receptors for migration factors in conditioned medium migrate into the root canal and cause pulp regeneration. Regenerative medicine is needed to restore the original function of complex tissues. To achieve this, it is necessary to reproduce the changes in the microenvironment of the host tissue that accompany the regenerative response. Therefore, it is important to reproduce the microenvironment <i>in vivo</i> for further development of tissue regeneration therapy. Periostin is also found in the epithelial–mesenchymal junction, with expression sites that differ depending on the mineralized matrix stage, and is involved in regulation of calcification. <i>Methods</i>. We investigate whether periostin contributes to microenvironmental changes in regenerated pulp tissue. Dental pulp stem cells were induced into dentin, and gene expression of DSPP, nestin, DMP1, Runx2, and periostin was analyzed by qPCR and protein expression by IHC. Similarly, gene expression was analyzed using qPCR and protein expression using IHC in regenerated dental pulp obtained by ectopic transplantation. <i>Results</i>. Since these regenerated tissues were observable on the same slice, it was possible to understand changes in the microenvironment within the tissues. <i>Conclusions</i>. Periostin promoted proliferation of pulp stem cells, migration in type I collagen, and calcification in regenerated pulp, which strongly suggests that periostin is a promising candidate as a factor that contributes to the microenvironment of regenerated pulp.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"11 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139945964","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}
Hongxia Tao, Qin Lv, Jing Zhang, Lijuan Chen, Yang Yang, Wei Sun
{"title":"Different Levels of Autophagy Activity in Mesenchymal Stem Cells Are Involved in the Progression of Idiopathic Pulmonary Fibrosis","authors":"Hongxia Tao, Qin Lv, Jing Zhang, Lijuan Chen, Yang Yang, Wei Sun","doi":"10.1155/2024/3429565","DOIUrl":"https://doi.org/10.1155/2024/3429565","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is an age-related lung interstitial disease that occurs predominantly in people over 65 years of age and for which there is a lack of effective therapeutic agents. It has demonstrated that mesenchymal stem cells (MSCs) including alveolar epithelial cells (AECs) can perform repair functions. However, MSCs lose their repair functions due to their distinctive aging characteristics, eventually leading to the progression of IPF. Recent breakthroughs have revealed that the degree of autophagic activity influences the renewal and aging of MSCs and determines the prognosis of IPF. Autophagy is a lysosome-dependent pathway that mediates the degradation and recycling of intracellular material and is an efficient way to renew the nonnuclear (cytoplasmic) part of eukaryotic cells, which is essential for maintaining cellular homeostasis and is a potential target for regulating MSCs function. Therefore, this review focuses on the changes in autophagic activity of MSCs, clarifies the relationship between autophagy and health status of MSCs and the effect of autophagic activity on MSCs senescence and IPF, providing a theoretical basis for promoting the clinical application of MSCs.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"27 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139766756","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}
Yang Ou, Yang Yang, Yan Wang, Heng Su, Yi-kun Zhou
{"title":"Effects of Extracellular Vesicles Derived from Human Umbilical Cord Blood Mesenchymal Stem Cells on Cell Immunity in Nonobese Mice","authors":"Yang Ou, Yang Yang, Yan Wang, Heng Su, Yi-kun Zhou","doi":"10.1155/2024/4775285","DOIUrl":"https://doi.org/10.1155/2024/4775285","url":null,"abstract":"Autoimmune responses are the most important pathogenic mechanisms underlying type 1 diabetes (T1D). Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have immunomodulatory effects. In this study, we investigated whether EVs derived from human umbilical cord MSCs (HucMSC-EVs) have treatment effects on nonobese diabetic (NOD) mice as model of T1D. HucMSC-EVs were isolated from human umbilical cord MSCs and characterized. NOD mice (aged 4 weeks) were administered with HucMSC-EVs or the same volume of phosphate-buffered saline (PBS) via caudal vein injection twice per week. After 8 weeks of treatment, blood, spleen, and pancreatic samples were collected. Mouse blood glucose levels and body weights were measured during treatment, and insulin concentration and inflammatory cytokine levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) staining were used to evaluate pathological changes in mouse islets. T lymphocyte subsets were evaluated by flow cytometry, while quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) analyses were used to detect the expression of transcription factor and inflammatory cytokines. Our data indicated that HucMSC-EVs treatment reduced blood glucose levels and increased insulin concentration in NOD mice. Levels of interleukin-2 (IL-2), IL-4, and IL-10 were significantly increased and those of IL-1<i>β</i> and interferon-<i>γ</i> (IFN-<i>γ</i>) significantly decreased in the HucMSC-EVs group. The positive ratio of CD4<sup>+</sup> T lymphocyte subsets decreased after intravenous injection of HucMSC-EVs, in which the proportion of Th2 cells increased and that of Th1 decreased. GATA-3 and IL-2, IL-4 and IL-10 expression levels were upregulated in spleen on treatment with HucMSC-EVs, whereas those of T-bet and IFN-<i>γ</i> were downregulated. In addition, more inflammatory cell infiltration was detected in the pancreas of control group mice than those treated with HucMSC-EVs. IHC staining showed that Fas/FasL expression and distribution in control group pancreas were higher than those in the HucMSC-EVs group. Together, our findings indicate that HucMSC-EVs have potential to prevent islet injury via T cell immune responses by adjusting the Th1/Th2 ratio to regulate secretion of inflammatory factors.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"10 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139668667","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 : 2024-01-31eCollection Date: 2024-01-01DOI: 10.1155/2024/9875640
Stem Cells International
{"title":"Retracted: Effect of Fas and Bcl-2 DNA Damages Response Expression in Stem Cells on Apoptosis of Nucleus Pulposus of Intervertebral Disc.","authors":"Stem Cells International","doi":"10.1155/2024/9875640","DOIUrl":"10.1155/2024/9875640","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.1155/2023/8103595.].</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"9875640"},"PeriodicalIF":4.3,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10849805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703488","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":"METTL3-Mediated m6A Modification Regulates the Osteogenic Differentiation through LncRNA CUTALP in Periodontal Mesenchymal Stem Cells of Periodontitis Patients","authors":"Xin Chen, Yuan Qin, Xian Wang, Hao Lei, Xiaochen Zhang, Houzhuo Luo, Changgang Guo, Weifu Sun, Shishu Fang, Wen Qin, Zuolin Jin","doi":"10.1155/2024/3361794","DOIUrl":"https://doi.org/10.1155/2024/3361794","url":null,"abstract":"<i>Objective</i>. Periodontitis is a chronic inflammatory disease that causes loss of periodontal support tissue. Our objective was to investigate the mechanism by which METTL3-mediated N6-methyladenosine modification regulates the osteogenic differentiation through lncRNA in periodontal mesenchymal stem cells in patients with periodontitis (pPDLSCs). <i>Material and Methods</i>. We carried out a series of experiments, including methylated RNA immunoprecipitation-PCR, quantitative real-time polymerase chain reaction, and western blotting. The expressions of alkaline phosphatase (ALP), Runx2, Col1, Runx2 protein level, ALP staining, and Alizarin red staining were used to demonstrate the degree of osteogenic differentiation. <i>Results</i>. We found that METTL3 was the most significantly differentially expressed methylation-related enzyme in pPDLSCs and promoted osteogenic differentiation of pPDLSCs. METTL3 regulated the stability and expression of lncRNA CUTALP, while lncRNA CUTALP promoted osteogenic differentiation of pPDLSCs by inhibiting miR-30b-3p. At different time points of osteogenic differentiation, lncRNA CUTALP expression was positively correlated with Runx2, while miR-30b-3p showed the opposite pattern. The attenuated osteogenic differentiation induced by <i>METTL3</i> knockdown was recovered by lncRNA CUTALP overexpression. The attenuated osteogenic differentiation induced by lncRNA CUTALP knockdown could be reversed by the miR-30b-3p inhibitor. <i>Conclusions</i>. In summary, METTL3/lncRNA CUTALP/miR-30b-3p/Runx2 is a regulatory network in the osteogenic differentiation of pPDLSCs.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"27 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139495269","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}