Stem Cells InternationalPub Date : 2024-10-24eCollection Date: 2024-01-01DOI: 10.1155/2024/7419270
Rui Zhai, Fumin Tai, Kexin Ding, Xin Tan, Hujie Li, Zhengyue Cao, Changhui Ge, Xiaofei Zheng, Hanjiang Fu
{"title":"Comparative Analysis of the Therapeutic Effects of MSCs From Umbilical Cord, Bone Marrow, and Adipose Tissue and Investigating the Impact of Oxidized RNA on Radiation-Induced Lung Injury.","authors":"Rui Zhai, Fumin Tai, Kexin Ding, Xin Tan, Hujie Li, Zhengyue Cao, Changhui Ge, Xiaofei Zheng, Hanjiang Fu","doi":"10.1155/2024/7419270","DOIUrl":"10.1155/2024/7419270","url":null,"abstract":"<p><p>Radiation-induced lung injury (RILI) is frequently observed in patients undergoing radiotherapy for thoracic malignancies, constituting a significant complication that hampers the effectiveness and utilization of tumor treatments. Ionizing radiation exerts both direct and indirect detrimental effects on cellular macromolecules, including DNA, RNA and proteins, but the impact of oxidized RNA in RILI remains inadequately explored. Mesenchymal stem cells (MSCs) can repair injured tissues, and the reparative potential and molecular mechanism of MSCs in treating RILI remains incompletely understood. This study aimed to investigate the therapeutic effects and mechanisms of action of three distinct sources of MSCs, including human umbilical cord mesenchymal stem cells (UCMSCs), bone marrow mesenchymal stem cells (BMSCs), and adipose-derived stem cells (ADSCs), in thoracically irradiated mice. Comparative analysis revealed that all three types of MSCs exhibited the ability to mitigate radiation-induced inflammatory infiltration, alveolar hemorrhage, and alveolar wall thickening in the lung tissue of the mice. MSCs also attenuated RILI by decreasing inflammatory factors, upregulating anti-inflammatory factor expression, and reducing collagen accumulation. Immunohistochemical results showed that all three MSCs reduced radiation-induced cell apoptosis and promoted the regeneration of lung tissue cells. The analysis of malondialdehyde (MDA) and 8-hydroyguanosine (8-OHG) content indicated that MSCs possess reparative properties against radiation-induced oxidative damage in lung tissue. The study provides evidence that UCMSCs are a more appropriate therapeutic option for RILI compared to BMSCs and ADSCs. Additionally, MSCs effectively reduce the accumulation of oxidized RNA in RILI, thereby, presenting a unique avenue for investigating the underlying mechanism of MSC-based treatment for RILI.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"7419270"},"PeriodicalIF":3.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558828","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":"IL-33-Pretreated Mesenchymal Stem Cells Attenuate Acute Liver Failure by Improving Homing and Polarizing M2 Macrophages.","authors":"Hui Yuan, Yuwen Li, Zihao Kong, Linya Peng, Jiali Song, Xiaoxue Hou, Wen Zhang, Rui Liu, Tiantong Feng, Chuanlong Zhu","doi":"10.1155/2024/1273099","DOIUrl":"10.1155/2024/1273099","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are highly effective in the treatment of acute liver failure (ALF). The efficacy of MSCs is closely related to the inflammatory environment. Therefore, we investigated the functional changes of MSCs in response to interleukin-33 (IL-33) stimulation. The results showed that bone marrow mesenchymal stem cells (BMSCs) pretreated with IL-33 had increased CCR2 expression, targeted CCL2 in the injured liver tissue, and improved the migration ability. Under LPS stimulation, the NF-<i>κ</i>B pathway of BMDM was activated, and its phenotype polarized to the M1-type, while BMSCs pretreated with IL-33 inhibited the NF-<i>κ</i>B pathway and enhanced M2 macrophage polarization. The M2-type macrophages could further inhibit hepatocytes inflammation, reduce hepatocytes apoptosis, and promote hepatocytes repair. These results suggest that IL-33 can enhance the efficacy of BMSCs in ALF and provide a new strategy for cell therapy of liver diseases.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"1273099"},"PeriodicalIF":3.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547550","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":"ANXA1 Enhances the Proangiogenic Potential of Human Dental Pulp Stem Cells.","authors":"Xiaocao Ma, Bichun Zhao, Chao Wang, Manqiang Sun, Yawen Dai, Lingling E, Mingzhu Gao, Xiangwei Liu, Yali Jia, Wen Yue, Hongchen Liu","doi":"10.1155/2024/7045341","DOIUrl":"10.1155/2024/7045341","url":null,"abstract":"<p><p>Dental trauma is highly prevalent in children and adolescents, alongside tooth decay. This condition mainly induces pulp contamination, pulp necrosis, and tooth avulsion in the clinical context. The disturbance to root growth is prone to occur in immature permanent teeth. However, conventional endodontic treatment may not achieve favorable outcomes in these cases, necessitating conducting relevant exploration. Therefore, this study was performed to examine the impact of Annexin A1 (ANXA1) on the vascular repair of dental pulp using human dental pulp stem cells (DPSCs). Specifically, RNA sequencing (RNA-Seq) and functional clustering analyses were employed to identify key genes involved in pulp regeneration. ANXA1 was detected in DPSCs and may correlate with pulp restoration. However, it remains undefined about the potential of ANXA1 to promote the angiogenetic differentiation of DPSCs. The results of this study revealed that the addition of ANXA1 significantly enhanced the secretion of vascular endothelial growth factor-A (VEGF-A) in DPSCs. Moreover, the incubation of DPSCs with ANXA1 resulted in a higher expression level of endothelial markers and promoted vessel formation through the upregulation of the phosphorylated p38 (p-p38) pathway. The in vivo results corroborated that the ANXA1 group exhibited more blood vessels and an increased ratio of positive staining for CD31. In conclusion, these findings indicate that ANXA1 enhances the in vivo and in vitro vascularization of DPSCs, and the activation of p-p38 may play a pivotal role in mediating the differentiation process.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"7045341"},"PeriodicalIF":3.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547549","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 : 2024-10-18eCollection Date: 2024-01-01DOI: 10.1155/2024/5176251
Talita D'Paula Tavares Pereira Muniz, Mariana Correa Rossi, Vânia Maria de Vasconcelos Machado, Ana Liz Garcia Alves
{"title":"Mesenchymal Stem Cells and Tissue Bioengineering Applications in Sheep as Ideal Model.","authors":"Talita D'Paula Tavares Pereira Muniz, Mariana Correa Rossi, Vânia Maria de Vasconcelos Machado, Ana Liz Garcia Alves","doi":"10.1155/2024/5176251","DOIUrl":"10.1155/2024/5176251","url":null,"abstract":"<p><p>The most common technologies in tissue engineering include growth factor therapies; metal implants, such as titanium; 3D bioprinting; nanoimprinting for ceramic/polymer scaffolds; and cell therapies, such as mesenchymal stem cells (MSCs). Cell therapy is a promising alternative to organ grafts and transplants in the treatment of numerous musculoskeletal diseases. MSCs have increasingly been used in generative medicine due to their specialized self-renewal, immunomodulation, multiplication, and differentiation properties. To further expand the potential of these cells in tissue repair, significant efforts are currently dedicated to the production of biomaterials with desirable short- and long-term biophysical properties that can aid the differentiation and expansion of MSCs. Biomaterials support MSC differentiation by modulating their characteristics, such as composition, mechanical properties, porosity, and topography. This review aimed to describe recent MSC approaches, including those associated with biomaterials, from experimental, clinical, and preclinical studies with sheep models.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"5176251"},"PeriodicalIF":3.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508286","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 : 2024-10-03eCollection Date: 2024-01-01DOI: 10.1155/2024/7084913
Mojtaba Sargazi, Narges Karbalaei, Saied Karbalay-Doust, Sara Keshtgar, Zohre Aghaei
{"title":"Wharton's Jelly Mesenchymal Stem Cell Conditioned Medium Ameliorates Diabetes-Induced Testicular Damage and Sperm Abnormalities by Mitigating Oxidative Stress, Apoptosis, and Inflammation.","authors":"Mojtaba Sargazi, Narges Karbalaei, Saied Karbalay-Doust, Sara Keshtgar, Zohre Aghaei","doi":"10.1155/2024/7084913","DOIUrl":"10.1155/2024/7084913","url":null,"abstract":"<p><p>Diabetes leads to testicular damage and infertility. Mesenchymal stem cells and their secretory trophic factors have shown potential as regenerative therapies for diabetes and its associated complications. This study examined the effects of conditioned medium derived from Wharton's jelly mesenchymal stem cells (WJMSCs-CM) on sperm parameters, reproductive hormones, biochemical parameters, and histological changes in the testes of diabetic rats. Fifty-six male Sprague-Dawley rats (250-300 g) were assigned to eight groups: control, diabetes, and six diabetic groups receiving early or late treatments with WJMSCs-CM (D-CM<sub>E</sub>, D-CM<sub>L</sub>), insulin (D-INS<sub>E</sub>, D-INS<sub>L</sub>), or DMEM (D-DM<sub>E</sub>, D-DM<sub>L</sub>). In the early treatment groups, insulin (3 U/day, subcutaneously) and WJMSCs-CM (10 mg/week, intraperitoneally) were administered immediately after diabetes induction; in the late treatment groups, these interventions began 30 days postinduction. Blood glucose and insulin levels, along with sperm parameters, were assessed. Sex hormones, testicular antioxidant enzyme activity, malondialdehyde (MDA), and glutathione (GSH) concentrations were measured using colorimetric methods. Real-time PCR detected Bax, Bcl-2, and tumor necrosis factor-alpha (TNF-<i>α</i>) gene expression. Our results showed that diabetes increased blood glucose levels, decreased insulin and sex hormone levels, induced testicular oxidative stress and apoptosis, and reduced sperm parameters compared to the control. WJMSCs-CM significantly ameliorated hyperglycemia, increased insulin and sex hormone levels, and improved sperm quality. In WJMSCs-CM-treated diabetic rats, MDA levels were reduced, while GSH and antioxidant enzyme activity increased. Furthermore, WJMSCs-CM decreased the testicular Bax/Bcl-2 ratio and TNF-<i>α</i> expression, as well as enhanced spermatogenic, Sertoli, and Leydig cells. In conclusion, WJMSC-CM administration effectively mitigated diabetes-induced testicular damage by reducing oxidative stress, inflammation, and apoptosis. Early treatment with WJMSCs-CM was more effective than late treatment for diabetes-induced reproductive dysfunction.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"7084913"},"PeriodicalIF":3.8,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401378","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":"Advancements and Innovative Strategies in Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cell Therapy: A Comprehensive Review.","authors":"Xiaoyu Shi, Kun Zhang, Fengshi Yu, Qi Qi, Xiaoyu Cai, Yu Zhang","doi":"10.1155/2024/4073485","DOIUrl":"https://doi.org/10.1155/2024/4073485","url":null,"abstract":"<p><p>The effectiveness and safety of mesenchymal stem cell (MSC) therapy have been substantiated across various diseases. Nevertheless, challenges such as the restricted <i>in vitro</i> expansion capacity of tissue-derived MSCs and the clinical instability due to the high heterogeneity of isolated cells require urgent resolution. The induced pluripotent stem cell-derived MSCs (iPSC-MSCs), which is differentiated from iPSCs via specific experimental pathways, holds considerable potential as a substitute for tissue derived MSCs. Multiple studies have demonstrated that iPSCs can be differentiated into iPSC-MSCs through diverse differentiation strategies. Research suggests that iPSC-MSCs, when compared to tissue derived MSCs, exhibit superior characteristics in terms of proliferation ability, immune modulation capacity, and biological efficiency. In this review, we meticulously described and summarized the experimental methods of iPSC differentiation into iPSC-MSCs, the application of iPSC-MSCs in various disease models, the latest advancements in clinically relevant iPSC-derived cell products, and the development strategies for the next generation of iPSC-derived therapy products (not only cell products but also their derivatives).</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"4073485"},"PeriodicalIF":3.8,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393478","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 : 2024-09-28eCollection Date: 2024-01-01DOI: 10.1155/2024/1823163
Mengyu Wu, Jing Liu, Shu Zhang, Yi Jian, Ling Guo, Huacai Zhang, Junwei Mi, Guoxin Qu, Yaojun Liu, Chu Gao, Qingli Cai, Dalin Wen, Di Liu, Jianhui Sun, Jianxin Jiang, Hong Huang
{"title":"Shh Signaling from the Injured Lung Microenvironment Drives BMSCs Differentiation into Alveolar Type II Cells for Acute Lung Injury Treatment in Mice.","authors":"Mengyu Wu, Jing Liu, Shu Zhang, Yi Jian, Ling Guo, Huacai Zhang, Junwei Mi, Guoxin Qu, Yaojun Liu, Chu Gao, Qingli Cai, Dalin Wen, Di Liu, Jianhui Sun, Jianxin Jiang, Hong Huang","doi":"10.1155/2024/1823163","DOIUrl":"10.1155/2024/1823163","url":null,"abstract":"<p><p>Alveolar type II (AT2) cells are key effector cells for repairing damaged lungs. Direct differentiation into AT2 cells from bone marrow mesenchymal stem cells (BMSCs) is a promising approach to treating acute lung injury (ALI). The mechanisms of BMSC differentiation into AT2 cells have not been determined. The Sonic Hedgehog (Shh) pathway is involved in regulating multiple differentiation of MSCs. However, the role of the Shh pathway in mediating the differentiation of BMSCs into AT2 cells remains to be explored. The results showed that BMSCs significantly ameliorated lung injury and improved pulmonary function in mice with ALI. These improvements were accompanied by a relatively high proportion of BMSCs differentiate into AT2 cells and an increase in the total number of AT2 cells in the lungs. Lung tissue extracts from mice with ALI (ALITEs) were used to mimic the injured lung microenvironment. The addition of ALITEs significantly improved the differentiation efficiency of BMSCs into AT2 cells along with activation of the Shh pathway. The inhibition of the Shh pathway not only reduced the differentiation rate of BMSCs but also failed to mitigate lung injury and regenerate AT2 cells. The results confirmed that promoting AT2 cell regeneration through the differentiation of BMSCs into AT2 cells is one of the important therapeutic mechanisms for the treatment of ALI with BMSCs. This differentiation process is highly dependent on Shh pathway activation in BMSCs in the injured lung microenvironment.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"1823163"},"PeriodicalIF":3.8,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11455595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381659","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":"Research Status and Trends in Periodontal Ligament Stem Cells: A Bibliometric Analysis over the Past Two Decades.","authors":"Zhengyang Li, Jinyi Li, Shanshan Dai, Ruirui Liu, Qingyu Guo, Fei Liu","doi":"10.1155/2024/9955136","DOIUrl":"10.1155/2024/9955136","url":null,"abstract":"<p><strong>Objective: </strong>Currently, the summaries of research on periodontal ligament stem cells (PDLSCs) are mainly reviews, and the systematic evaluation of all relevant studies is lacking. The aim of our study was to reveal the research status and developmental trends of PDLSCs using bibliometric analyses.</p><p><strong>Methods: </strong>Publications on PDLSC from 2004 to 2023 in the PubMed database were searched and then screened according to certain inclusion and exclusion criteria. Two researchers browsed the included papers and recorded information such as the research type and research model. The VOSviewer software was used to analyze the distribution of authors, journals, and institutions. The contents and directions of PDLSC research were summarized by analyzing high-frequency keywords. The CiteSpace software was used to monitor burst words, determine hot factors, and indicate developmental trends.</p><p><strong>Results: </strong>During the past two decades, the number of studies on PDLSCs increased. China published the most related papers. The primary type of article was basic research. Among core journals, the <i>Journal of Periodontal Research</i> had the highest number of publications. The Fourth Military Medical University (China) was leading in the number of articles on PDLSCs. Research topics mainly included mechanism of periodontal diseases, tissue engineering and regeneration, biological characteristics of PDLSCs, and comparison with other stem cells. Infectious inflammation and mechanical stimulation were important pathological conditions and research topics.</p><p><strong>Conclusion: </strong>The research of PDLSCs is still in a rapid development stage. Our study provides new insights into the current research status and future trend in this field.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"9955136"},"PeriodicalIF":3.8,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381658","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":"Astragaloside IV Treats Parkinson's Disease by Regulating the Proliferation and Differentiation of NSCs through the SHH-Nurr1 Pathway.","authors":"Zicong Wu,Jianing Zhang,Han Gao,Wentao Li","doi":"10.1155/2024/2792909","DOIUrl":"https://doi.org/10.1155/2024/2792909","url":null,"abstract":"Recently, there has been a surge of interest in enhancing the differentiation of neural stem cells (NSCs) and supplementing dopamine neurons as a potential treatment for Parkinson's disease, the second most prevalent neurodegenerative disorder. Two factors, sonic hedgehog (SHH) and nuclear receptor-related 1 protein (Nurr1), have been identified as influential in NSCs differentiation. Additionally, Astragaloside IV (AS-IV), an active compound derived from Astragalus, has also been discovered to impact NSCs differentiation. To assess the effects of AS-IV on cell activity, CCK-8 and flow cytometry techniques were employed. Meanwhile, western blotting, immunofluorescence, and real-time PCR were utilized to detect protein expression both in vivo and in vitro. Furthermore, siRNA assay was used to verify the association between SHH and Nurr1 and to investigate whether AS-IV exerts its effects through this pathway. The experimental findings revealed that AS-IV enhances cell activity and promotes the expression of differentiation proteins related to NSCs. Furthermore, the relationship between the SHH-Nurr1 pathway was confirmed, demonstrating that AS-IV induces NSCs differentiation via this pathway. Consequently, SHH, acting as the upstream signaling pathway of Nurr1, influences its expression, while AS-IV regulates the proliferation and differentiation of NSCs by modulating the SHH-Nurr1 pathway.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"57 1","pages":"2792909"},"PeriodicalIF":4.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142191535","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 : 2024-08-29eCollection Date: 2024-01-01DOI: 10.1155/2024/5789593
Miaomiao Dai, Weisheng Hong, Yi Ouyang
{"title":"Identification and Validation of Hub Genes and Construction of miRNA-Gene and Transcription Factor-Gene Networks in Adipogenesis of Mesenchymal Stem Cells.","authors":"Miaomiao Dai, Weisheng Hong, Yi Ouyang","doi":"10.1155/2024/5789593","DOIUrl":"10.1155/2024/5789593","url":null,"abstract":"<p><strong>Background: </strong>Adipogenic differentiation stands as a crucial pathway in the range of differentiation options for mesenchymal stem cells (MSCs), carrying significant importance in the fields of regenerative medicine and the treatment of conditions such as obesity and osteoporosis. However, the exact mechanisms that control the adipogenic differentiation of MSCs are not yet fully understood.</p><p><strong>Materials and methods: </strong>We procured datasets, namely GSE36923, GSE80614, GSE107789, and GSE113253, from the Gene Expression Omnibus database. These datasets enabled us to perform a systematic analysis, including the identification of differentially expressed genes (DEGs) pre- and postadipogenic differentiation in MSCs. Subsequently, we conducted an exhaustive analysis of DEGs common to all four datasets. To gain further insights, we subjected these overlapped DEGs to comprehensive gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Following the construction of protein-protein interaction (PPI) networks, we meticulously identified a cohort of hub genes pivotal to the adipogenic differentiation process and validated them using real-time quantitative polymerase chain reaction. Subsequently, we ventured into the construction of miRNA-gene and TF-gene interaction networks.</p><p><strong>Results: </strong>Our rigorous analysis revealed a total of 18 upregulated DEGs and 12 downregulated DEGs that consistently appeared across all four datasets. Notably, the peroxisome proliferator-activated receptor signaling pathway, regulation of lipolysis in adipocytes, and the adipocytokine signaling pathway emerged as the top-ranking pathways significantly implicated in the regulation of these DEGs. Subsequent to the construction of the PPI network, we identified and validated 10 key node genes, namely IL6, FABP4, ADIPOQ, LPL, PLIN1, RBP4, ACACB, NT5E, KRT19, and G0S2. Our endeavor to construct miRNA-gene interaction networks led to the discovery of the top 10 pivotal miRNAs, including hsa-mir-27a-3p, hsa-let-7b-5p, hsa-mir-1-3p, hsa-mir-124-3p, hsa-mir-155-5p, hsa-mir-16-5p, hsa-mir-101-3p, hsa-mir-21-3p, hsa-mir-146a-5p, and hsa-mir-148b-3p. Furthermore, the construction of TF-gene interaction networks revealed the top 10 critical TFs: ZNF501, ZNF512, YY1, EZH2, ZFP37, ZNF2, SOX13, MXD3, ELF3, and TFDP1.</p><p><strong>Conclusions: </strong>In summary, our comprehensive study has successfully unraveled the pivotal hub genes that govern the adipogenesis of MSCs. Moreover, the meticulously constructed miRNA-gene and TF-gene interaction networks are poised to significantly augment our comprehension of the intricacies underlying MSC adipogenic differentiation, thus providing a robust foundation for future advances in regenerative biology.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"5789593"},"PeriodicalIF":3.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141101","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}