Stem Cells International最新文献

{"title":"Narrative Review of Mesenchymal Stem Cell Therapy in Renal Diseases: Mechanisms, Clinical Applications, and Future Directions.","authors":"Yanjun Wang, Pengli Luo, Tana Wuren","doi":"10.1155/sci/8658246","DOIUrl":"https://doi.org/10.1155/sci/8658246","url":null,"abstract":"<p><p>Renal diseases, particularly acute kidney injury (AKI) and chronic kidney disease (CKD), are significant global health challenges. These conditions impair kidney function and can lead to serious complications, including cardiovascular diseases, which further exacerbate the public health burden. Currently, the global AKI mortality rate is alarmingly high (20%-50%); CKD is projected to emerge as a major global health burden by 2040. Existing treatments such as hemodialysis and kidney transplantation have limited effectiveness and are often associated with adverse effects. Mesenchymal stem cells (MSCs) offer considerable potential for treating renal diseases owing to their regenerative and immunomodulatory properties. Thus, this review focuses on the application of MSCs in renal disease, discusses fundamental research findings, and evaluates their application in clinical trials. Moreover, we discuss the impact and safety of MSCs as a therapeutic option and highlight challenges and potential directions for their clinical application. We selected research articles from PubMed published within the last 5 years (from 2019), focusing on high-impact journals and clinical trial data, and included a few key studies predating 2019. Considerations included the novelty of the research, sample size, experimental design, and data reliability. With advancements in single-cell sequencing, CRISPR/Cas9 gene editing, and other cutting-edge technologies, future MSC research will explore combination therapies and personalized treatments to provide more promising, safer treatments with reduced adverse reactions and enhanced therapeutic outcomes. These advances will improve kidney disease treatment methods, enhance patient quality of life, and maximize the benefits of MSC therapies.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"8658246"},"PeriodicalIF":3.8,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142855344","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":"Human iPSC-Derived Endothelial Cells Exhibit Reduced Immunogenicity in Comparison With Human Primary Endothelial Cells.","authors":"Haiyan Jia, Melanie Moore, Meenu Wadhwa, Chris Burns","doi":"10.1155/sci/6153235","DOIUrl":"https://doi.org/10.1155/sci/6153235","url":null,"abstract":"<p><p>Human induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) have emerged as a promising source of autologous cells with great potential to produce novel cell therapy for ischemic vascular diseases. However, their clinical application still faces numerous challenges including safety concerns such as the potential aberrant immunogenicity derived from the reprogramming process. This study investigated immunological phenotypes of iPSC-ECs by a side-by-side comparison with primary human umbilical vein ECs (HUVECs). Three types of human iPSC-ECs, NIBSC8-EC generated in house and two commercial iPSC-ECs, alongside HUVECs, were examined for surface expression of proteins of immune relevance under resting conditions and after cytokine activation. All iPSC-EC populations failed to express major histocompatibility complex (MHC) Class II on their surface following interferon-gamma (IFN-<i>γ</i>) treatment but showed similar basal and IFN-<i>γ</i>-stimulated expression levels of MHC Class I of HUVECs. Multiple iPSC-ECs also retained constitutive and tumor necrosis factor-alpha (TNF-<i>α</i>)-stimulated expression levels of intercellular adhesion molecule-1 (ICAM-1) like HUVECs. However, TNF-<i>α</i> induced a differential expression of E-selectin and vascular cell adhesion molecule-1 (VCAM-1) on iPSC-ECs. Furthermore, real-time monitoring of proliferation of human peripheral blood mononuclear cells (PBMCs) cocultured on an endothelial monolayer over 5 days showed that iPSC-ECs provoked distinct dynamics of PBMC proliferation, which was generally decreased in alloreactivity and IFN-<i>γ</i>-stimulated proliferation of PBMCs compared with HUVECs. Consistently, in the conventional mixed lymphocyte reaction (MLR), the proliferation of total CD3+ and CD4+ T cells after 5-day cocultures with multiple iPSC-EC populations was largely reduced compared to HUVECs. Last, multiple iPSC-EC cocultures secreted lower levels of proinflammatory cytokines than HUVEC cocultures. Collectively, iPSC-ECs manifested many similarities, but also some disparities with a generally weaker inflammatory immune response than primary ECs, indicating that iPSC-ECs may possibly exhibit hypoimmunogenicity corresponding with less risk of immune rejection in a transplant setting, which is important for safe and effective cell therapies.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"6153235"},"PeriodicalIF":3.8,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839903","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":"Conditioned Medium Derived From Human Dental Follicle Mesenchymal Stem Cells Alleviates Macrophage Proinflammatory Responses Through MAPK-ERK-EGR1 Axis.","authors":"Chuhan Zhang, Peiyi Lv, Qiuying Liang, Jian Zhou, Buling Wu, Wenan Xu","doi":"10.1155/sci/5514771","DOIUrl":"10.1155/sci/5514771","url":null,"abstract":"<p><p>The regulation of macrophage polarization by mesenchymal stem cells (MSCs) is a prominent area of research but faces challenges due to limited MSC sources and incomplete understanding of underlying mechanisms. We sought to identify an accessible MSC source and investigate how MSCs regulate macrophage polarization using high-throughput sequencing. We isolated dental follicle MSCs from discarded human third molar dental follicles and cocultured them with THP-1-derived macrophages in the conditioned medium. Transcriptome sequencing identified differentially expressed genes (DEGs) in macrophages, integrating with multiomics database analysis to uncover polarization mechanisms. Our findings demonstrated successful MSC extraction from dental follicles, with the conditioned medium suppressing proinflammatory macrophage functions and influencing macrophage subtyping. MSCs, through paracrine signaling, activated the mitogen-activated protein kinase (MAPK) pathway, leading to extracellular regulated protein kinases (ERK)1/2 phosphorylation and upregulation of early growth response 1 (EGR1) protein. Elevated EGR1 levels inhibited inflammatory gene expression, inhibiting the pro-inflammatory immunoregulatory function of macrophages in inflammatory states. This study provides an efficient method for in vitro macrophage polarization identification. It offers insights into MSC-regulated polarization mechanisms, with potential clinical implications for anti-inflammatory therapy and immune regulation.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"5514771"},"PeriodicalIF":3.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11623994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802279","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":"Long Noncoding RNA EMX2-AS Facilitates Osteoblast Differentiation and Bone Formation by Inhibiting EMX2 Protein Translation and Activating Wnt/<i>β</i>-Catenin Pathway.","authors":"Linyuan Fan, Li Zhang, Xin Zhang, Wei Wei, Zhaohui Liu","doi":"10.1155/sci/4397807","DOIUrl":"10.1155/sci/4397807","url":null,"abstract":"<p><p>Long noncoding RNAs (lncRNAs), as a potentially new and crucial element of biological regulation, have gained widespread attention in recent years. Our previous work identified lncRNA empty spiracles homeobox 2 antisence (EMX2-AS) was significantly increased during the osteoblast differentiation of mesenchymal stem cells (MSCs). Overexpression of lncRNA EMX2-AS promoted osteogenesis in vitro and enhanced heterotopic bone formation in vivo, whereas lncRNA EMX2-AS knockdown had the opposite effect. EMX2 could negatively regulate the osteoblast differentiation of MSCs. lncRNA EMX2-AS was 80% expressed in the cytoplasm during osteoblast differentiation in MSCs. Mechanistic analysis revealed that lncRNA EMX2-AS acts as a positive regulator of osteogenic differentiation through interaction with EMX2 and suppression of its expression at the translational level and Wnt/<i>β</i>-catenin pathway is involved in lncRNA EMX2-AS/EMX2 regulated osteogenic differentiation. Our findings not only provide new targets for the treatment of diseases related to osteoblast differentiation disruption but also enrich the understanding of the regulation mechanisms of lncRNA during stem cell differentiation.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"4397807"},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772395","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":"Identification of a Novel Mesenchymal Stem Cell-Related Signature for Predicting the Prognosis and Therapeutic Responses of Bladder Cancer.","authors":"Enguang Yang, Luhua Ji, Xinyu Zhang, Suoshi Jing, Pan Li, Hanzhang Wang, Luyang Zhang, Yuanfeng Zhang, Li Yang, Junqiang Tian, Zhiping Wang","doi":"10.1155/sci/6064671","DOIUrl":"https://doi.org/10.1155/sci/6064671","url":null,"abstract":"<p><p><b>Background:</b> Mesenchymal stem cells (MSCs) have been identified to have a unique migratory pattern toward tumor sites across diverse cancer types, playing a crucial role in cancer progression, treatment resistance, and immunosuppression. This study aims to formulate a prognostic model focused on MSC-associated markers to efficiently predict the clinical outcomes and responses to therapy in individuals with bladder cancer (BC). <b>Methods:</b> Clinical and transcriptome profiling data were extracted from The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA-BLCA) and GSE31684 databases. Systematic quantification of MSC prevalences and stromal indices was undertaken, culminating in the discernment of genes correlated with stromal MSCs following a thorough application of weighted gene coexpression network analysis techniques. Subsequently, an exhaustive risk signature pertinent to MSC was formulated by amalgamating methods from univariate and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression models. Drugs targeting genes associated with MSCs were screened using molecular docking. <b>Results:</b> The prognostic model for MSC incorporated five critical genes: ZNF165, matrix remodeling-associated 7 (MXRA7), CEMIP, ADP-ribosylation factor-like 4C (ARL4C), and cerebral endothelial cell adhesion molecule (CERCAM). In the case of BC patients, stratification was performed into discrete risk categories, utilizing the median MSC risk score as a criterion. It was striking that those classified within the high-MSC-risk bracket demonstrated correlations with unfavorable prognostic implications. Enhanced responsiveness to immunotherapy in low-MSC-risk patients was delineated compared to their high-MSC-risk counterparts. A heightened receptivity was noted toward particular chemotherapy drugs, encompassing gemcitabine, vincristine, paclitaxel, gefitinib, and sorafenib, within this high-risk group. Conversely, a superior reaction to cisplatin was distinctly evident among those marked by low MSC scores. The results of molecular docking demonstrated that kaempferol exhibited favorable docking with ZNF165, quercetin exhibited favorable docking with MXRA7, mairin exhibited favorable docking with CEMIP, and limonin diosphenol exhibited favorable docking with ARL4C. <b>Conclusions:</b> The five-gene MSC prognostic model demonstrates substantial efficacy in prognosticating clinical outcomes and gauging responsiveness to chemotherapy and immunotherapy regimens. The genes ZNF165, MXRA7, CEMIP, ARL4C, and CERCAM are underscored as promising candidates warranting further exploration for anti-MSC therapeutic strategies, thereby offering novel insights for personalized treatment approaches in BC.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2024 ","pages":"6064671"},"PeriodicalIF":3.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11611448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772475","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":"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}

{"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}

{"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_E, D-CM_L), insulin (D-INS_E, D-INS_L), or DMEM (D-DM_E, D-DM_L). 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}