World journal of stem cells最新文献

{"title":"Efficacy and safety of umbilical cord-derived mesenchymal stem cell-conditioned media for preventing and treating skin aging.","authors":"Hyunjun Ahn, Ho-Seong Han, Kye-Ho Lee","doi":"10.4252/wjsc.v17.i9.108049","DOIUrl":"10.4252/wjsc.v17.i9.108049","url":null,"abstract":"<p><strong>Background: </strong>Research has been increasingly conducted on the connection between mesenchymal stem cell (MSC)-conditioned medium (MSC-CM) and aging. However, most studies have focused on adipose-derived MSC-CM (ADMSC-CM), resulting in a research bias. We hypothesized that umbilical cord-derived MSCs, being younger than adipose-derived MSCs, would be more suitable for overcoming aging-related processes.</p><p><strong>Aim: </strong>To assess the efficacy and safety of umbilical cord-derived MSC-CM (UCMSC-CM) for preventing and treating skin aging.</p><p><strong>Methods: </strong><i>In vitro</i> and <i>in vivo</i> studies were conducted to compare UCMSC-CM with ADMSC-CM, the most studied active aging-preventive conditioned medium to date. Additionally, the most effective delivery method of UCMSC-CM for aged skin was identified.</p><p><strong>Results: </strong>UCMSC-CM had a higher content of effective factors, stimulated higher proliferation of fibroblasts, and strongly inhibited melanin production in B16F1 cells. In aged mice, UCMSC-CM application increased skin thickness, the number of Ki-67-positive cells, and the area of collagen deposition. UCMSC-CM was more effective than ADMSC-CM in preventing and treating skin aging. Additionally, a safety evaluation of UCMSC-CM performed in various animal models indicated that it was safe even when used directly on the skin.</p><p><strong>Conclusion: </strong>UCMSC-CM is effective and safe for preventing and treating skin aging.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 9","pages":"108049"},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192904","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":"Bone marrow mesenchymal stem cell-derived exosomal lactate dehydrogenase A promotes tendon-bone healing <i>via</i> histone lactylation-mediated cartilage regeneration.","authors":"Ting Zhang, Qing Huang, Kai-Feng Gan","doi":"10.4252/wjsc.v17.i9.106282","DOIUrl":"10.4252/wjsc.v17.i9.106282","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Anterior cruciate ligament reconstruction (ACLR) is the dominant clinical modality for the treatment of anterior cruciate ligament injuries. The success of ACLR is largely dependent on tendon-bone healing, and stem cell biotherapies are often used to facilitate this process. Histone lactylation modifications are involved in the regulation of various diseases. Lactate dehydrogenase A (LDHA) has been shown to play an important role in exosomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;To explore the regulation of tendon-bone healing after ACLR by LDHA in exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;BMSC-Exos and LDHA were characterized and analyzed by transmission electron microscopy, qNano, immunofluorescence and western blotting assay. The corresponding low expression cell lines were obtained using RNA interference transfection; LDHA expression in rat bone tissues after ACLR was analyzed by western blotting. The volume of newborn bone tissues was monitored by micro-computed tomography imaging. Tendon and fibrocartilage regeneration were further analyzed and calculated by histological analysis, including hematoxylin and eosin and Safranin O-Fast green staining, respectively; LDHA levels of chondrocyte stem cells (CSPCs) after co-incubation with BMSC-Exos were analyzed by western blotting. Extracellularly secreted lactic acid content was determined by lactate assay kit. Cell viability was assessed by cell counting kit 8 assay, and the proliferation and differentiation ability of cells was further examined by the expression of collagen II, SOX9 and aggrecan. Histone H3K18 lactylation modification was analyzed by western blotting. H3K18 La binding on bone morphogenetic protein 7 (BMP7) promoter was analyzed by chromatin immunoprecipitation-quantitative polymerase chain reaction; BMP7 promoter activity was analyzed by dual luciferase reporter gene; BMP7 protein expression was analyzed using quantitative polymerase chain reaction and western blotting. Then, the proliferation of CSPCs promoted by BMSC-Exos LDHA was analyzed by protein expression levels of LDHA, BMP7, collagen II, SOX9, aggrecan, extracellular lactate content, and cell counting kit 8 assay.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The spherical nanosized BMSC-Exos could be uptaken by CSPCs. LDHA was highly expressed in BMSC-Exos, which could infiltrate into the bone tissue of ACLR rats and promoted the generation of new bone tissue, as well as significantly increased the regeneration of tendon and fibrocartilage. Co-incubation of CSPCs with high-expressing LDHA BMSC-Exos increased the secretion of lactate content from CSPCs, cell viability, and the expression of markers related to cell proliferation and differentiation, including collagen II, SOX9, and aggrecan; LDHA in BMSC-Exos upregulated BMP7 through histone H3K18 lactate modification; high LDHA expression reversed the knockdown of BMP7, further increasing the prolife","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 9","pages":"106282"},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193318","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":"Dual role and clinical application of extracellular vesicles in acute respiratory distress syndrome: Mechanism analysis and translational challenges.","authors":"Yi-Fu Tie, Han Liu, Tong Zhang, Tian-Wei Meng, Qun Liang","doi":"10.4252/wjsc.v17.i9.108657","DOIUrl":"10.4252/wjsc.v17.i9.108657","url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS) is a severe and life-threatening manifestation of acute lung injury, characterized by widespread pulmonary inflammation and edema, ultimately resulting in acute respiratory failure. Despite advancements in mechanical ventilation and lung-protective strategies, targeted therapies aimed at modulating dysregulated inflammation and promoting tissue repair remain elusive. Extracellular vesicles (EVs), critical mediators of intercellular communication, have emerged as a promising research focus due to their dual regulatory roles in ARDS pathogenesis. Pro-inflammatory EVs, derived from pathogens or injury-stressed cells, exacerbate alveolar macrophage activation and increase endothelial permeability, thereby aggravating pulmonary damage. In contrast, anti-inflammatory EVs originating from mesenchymal stem cells facilitate alveolar barrier restoration and tissue repair by delivering reparative molecular cargo. This review systematically evaluates the dualistic functions of EVs in ARDS from three key perspectives: Molecular mechanisms, clinical translation, and technical challenges. We further discuss the complexities associated with EV heterogeneity, pathogen interactions, and standardization in EV production. Additionally, we propose future directions that integrate engineered EV modifications and multi-omics approaches to address current therapeutic limitations and enhance ARDS management.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 9","pages":"108657"},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192926","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":"Wumei Pills enhance intestinal stem cell - mediated repair in chemotherapy-induced mucositis <i>via Lactobacillus reuteri</i> - dependent modulation of the gut microbiota.","authors":"Dong-Xue Lu, Zi-Xuan Wang, Xi-Min Liu, Hua Wu, Li-Jiang Ji, Jing Yan","doi":"10.4252/wjsc.v17.i9.107025","DOIUrl":"10.4252/wjsc.v17.i9.107025","url":null,"abstract":"<p><strong>Background: </strong>Intestinal mucositis is a severe and common complication of chemotherapy, characterized by disruption of the gut microbiota, intestinal inflammation, and epithelial barrier damage. Intestinal stem cells (ISCs) are essential for epithelial renewal and barrier maintenance, yet chemotherapy impairs ISC proliferation and function, delaying mucosal repair. We hypothesized that Wumei Pills (WMP) could protect against chemotherapy-induced intestinal mucositis by modulating gut microbiota - particularly <i>Lactobacillus reuteri</i> (<i>L. reuteri</i>) - to restore ISC activity, preserve microbial balance, reduce inflammation, and promote epithelial regeneration.</p><p><strong>Aim: </strong>To characterize these changes and the safety of WMP <i>via</i> a 5-fluorouracil (5-FU) induced intestinal mucositis mouse model.</p><p><strong>Methods: </strong>In this study, we established a 5-FU induced intestinal mucositis mouse model, to explore the protective effect of WMP regulating <i>L. reuteri</i> on integrity of intestinal mucosa.</p><p><strong>Results: </strong>We found that intestinal flora is an important mechanism causing chemotherapy-induced intestinal mucositis, but WMP and live <i>L. reuteri</i> were effective in protecting the morphology of intestinal mucositis and normal proliferation of epithelial. <i>L. reuteri</i> colonized in the intestinal mucosa and WMP ameliorated intestinal mucosa damage caused by 5-FU treatment, including improvement of body weight, pathological change, and proliferation level, reducement proinflammatory cytokine secretion (tumor necrosis factor-α, interleukin-6) and the lipopolysaccharides concentration in serum. The repair process stimulated by both <i>L. reuteri</i> and WMP were also accompanied with increased leucine-rich-repeat-containing G-protein-coupled receptor 5 (+) and proliferating cell nuclear antigen of mice intestine. Furthermore, we demonstrated that WMP and <i>L. reuteri</i> activated the Wingless-type/β-catenin pathway to accelerate proliferation of intestinal epithelial, thus recovering damaged intestinal mucosa. However, the relieving effect of <i>L. reuteri</i> on intestinal mucosa was inferior to that of WMP.</p><p><strong>Conclusion: </strong>Our findings indicate that WMP regulating <i>L. reuteri</i> protects intestinal barrier and activates intestinal epithelial proliferation, which sheds light on treatment approaches for intestinal inflammation based on ISCs with traditional Chinese medicine and probiotics <i>L. reuteri</i>.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 9","pages":"107025"},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193361","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":"Stem cell-based cartilage regeneration: Biological strategies, engineering innovations, and clinical translation.","authors":"Bo Cong, Feng-Hua Zhang, Hai-Guang Zhang","doi":"10.4252/wjsc.v17.i9.108523","DOIUrl":"10.4252/wjsc.v17.i9.108523","url":null,"abstract":"<p><p>Articular cartilage damage caused by trauma or degenerative diseases such as osteoarthritis remains a major therapeutic challenge due to the tissue's limited regenerative capacity. Traditional surgical interventions-including microfracture, autologous chondrocyte implantation, and osteochondral grafting-often result in the formation of biomechanically inferior fibrocartilage and fail to restore long-term joint function. In contrast, stem cell-based strategies have emerged as a promising approach for regenerating hyaline-like cartilage by combining the biological potential of mesenchymal stem cells and induced pluripotent stem cells with advances in tissue engineering. This review synthesizes the current understanding of cartilage structure and repair limitations, evaluates the regenerative potential of various stem cell sources, and highlights engineering innovations such as bioactive scaffolds, controlled growth factor delivery, and three-dimensional bioprinting. We also examine key preclinical studies and early-phase clinical trials demonstrating the safety and efficacy of stem cell-based therapies. Finally, we explore future directions, including gene editing, exosome-based therapeutics, and personalized regenerative strategies, that may address remaining translational barriers. Collectively, stem cell-centered approaches offer a transformative avenue toward durable, functional cartilage repair and hold strong potential for clinical application.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 9","pages":"108523"},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193353","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":"Expression of cancer stem cell markers and their prognostic significance in stage IIIA non-small cell lung cancer.","authors":"Tao Lin, Si-Cong Jiang, Xian-Ming He, Wen-Zhen Xu, Cai-Jin Jin, You-Dan Guo","doi":"10.4252/wjsc.v17.i9.106381","DOIUrl":"10.4252/wjsc.v17.i9.106381","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Non-small cell lung cancer (NSCLC) is the most prevalent subtype of lung cancer, accounting for approximately 85% of all lung cancer cases and remaining a major cause of cancer-related mortality worldwide. Despite advances in diagnostic and therapeutic approaches, the incidence and mortality rates of NSCLC continue to rise, especially in low-income and middle-income countries.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;To investigate the expression of cancer stem cell (CSC) markers and their relationship with the prognosis and survival of patients with stage IIIA NSCLC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A retrospective analysis was conducted on the clinical data and survival follow-up information of 61 patients with stage IIIA NSCLC treated at our hospital from February 2020 to June 2022, and all cases were confirmed as primary (non-recurrent) diagnoses based on clinical and pathological records. All patients were followed up through outpatient visits or telephone interviews. The follow-up duration ranged from 6 to 51 months with a median follow-up time of 36 months. Overall survival (OS) was defined as the time from the date of pathological diagnosis to death or the last follow-up. Univariate and multivariate Cox regression analyses were performed to examine the relationship between clinical characteristics and OS. Immunohistochemistry was used to detect the expression of CSC markers [octamer-binding transcription factor 4 (OCT4), trophoblast cell surface antigen-2 (TROP-2), ATP-binding cassette subfamily G member 2 (ABCG2), p75 neurotrophin receptor (p75NTR)] in NSCLC, followed by immunohistochemical scoring. The high H-scores of CSC markers, age, and micropapillary components were combined to generate a tumor stemness index (TSI). The Kaplan-Meier method was used to analyze the relationship between CSC markers, TSI, and OS in patients with NSCLC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Multivariate Cox regression analysis showed that age [hazard ratio (HR) = 1.952, 95% confidence interval (CI): 1.087-2.481, &lt;i&gt;P&lt;/i&gt; = 0.029] and micropapillary components (HR = 2.716, 95%CI: 1.259-5.837, &lt;i&gt;P&lt;/i&gt; = 0.013) were significantly associated with OS. In NSCLC there were 21 cases with high OCT4 H-scores, 27 cases with high TROP-2 H-scores, 44 cases with high ABCG2 H-scores, and 44 cases with high p75NTR H-scores. In the survival analysis the high OCT4 expression group had a poorer prognosis (&lt;i&gt;P&lt;/i&gt; = 0.006). Further subtype analysis revealed no statistically significant difference in OS between high and low OCT4 H-score groups in patients with lung squamous cell carcinoma (&lt;i&gt;P&lt;/i&gt; = 0.457). However, in patients with lung adenocarcinoma high OCT4 expression had significantly poorer OS compared with those with low OCT4 expression (&lt;i&gt;P&lt;/i&gt; = 0.005). TROP-2, ABCG2, and p75NTR did not significantly affect the prognosis. TSI was significantly associated with OS in patients with NSCLC (HR = 2.209, 95%CI: 1.238-3.681, &lt;i&gt;P&lt;/i&gt; = 0.027).&lt;/p&gt;&lt;p&gt;&lt;stron","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 9","pages":"106381"},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192882","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":"Post-translational modifications in osteogenic differentiation of oral-derived stem cells: Mechanisms and clinical implications.","authors":"Zhuo-Jin Shi, Wei Liu","doi":"10.4252/wjsc.v17.i9.109662","DOIUrl":"10.4252/wjsc.v17.i9.109662","url":null,"abstract":"<p><p>Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix, with oral-derived stem cells playing a significant role in this process. Various post-translational modifications (PTMs), such as phosphorylation, acetylation, methylation, and glycosylation, regulate osteogenic differentiation (OD). These modifications influence the expression of osteogenic genes by modulating the activity of key transcription factors like runt-related transcription factor 2 and osterix. While the molecular mechanisms behind OD are increasingly understood, many questions remain, particularly regarding how PTMs control the specificity and efficiency of stem cell differentiation. Recent research into these modifications has underscored the potential of stem cell therapy for bone regeneration and treating bone-related diseases. This review summarizes the role of PTMs in the OD of oral-derived stem cells, discusses their clinical applications, and suggests future research directions.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 9","pages":"109662"},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193245","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":"Quercetin pretreated umbilical cord mesenchymal stem cells alleviate inflammatory bowel disease <i>via</i> IL-10 /Janus kinase 2/STAT3 signaling.","authors":"Meng-Yue Shi, Lian Liu, Fu-Yuan Yang","doi":"10.4252/wjsc.v17.i9.105896","DOIUrl":"10.4252/wjsc.v17.i9.105896","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel disease (IBD) is a chronic, progressive inflammatory condition of the intestine. Mesenchymal stem cell (MSC) therapy for IBD has made significant progress in recent years. To better exploit the therapeutic potential of MSCs, pretreatment strategies are employed to enhance their therapeutic capabilities. As a compound with diverse pharmacological effects, quercetin (QUR) is applied to pretreat human umbilical cord-derived MSCs (hUCMSCs) in this study, thereby augmenting their immunotherapeutic potential.</p><p><strong>Aim: </strong>To evaluate the therapeutic efficacy of QUR-pretreated hUCMSCs.</p><p><strong>Methods: </strong>We induced colitis in a mouse model using a 2,4,6-trinitrobenzenesulfonic acid solution. Intraperitoneal injection of QUR-pretreated hUCMSCs significantly improved clinical and pathological manifestations of colitis compared to the model group. Interestingly, the therapeutic effect was superior to that of untreated hUCMSCs. Mice exhibited significantly reduced weight loss, diminished infiltration of inflammatory cells observed in hematoxylin and eosin staining, improved Disease Activity Index and Histological Activity Index scores. Furthermore, colonic tissue analysis revealed a significant upregulation of the anti-inflammatory cytokine interleukin 10 (IL-10), accompanied by a downregulation of the pro-inflammatory cytokine IL-6. Further tests also suggested that QUR pretreatment led to inhibition of Janus kinase/signal transducer and activator of transcription (STAT) phosphorylation.</p><p><strong>Results: </strong>Our study demonstrated that QUR pretreatment of hUCMSCs significantly enhanced their immune-regulatory capacity. This approach effectively mitigated colonic inflammation in a mouse colitis model by modulating the IL-10/Janus kinase/STAT signaling pathway.</p><p><strong>Conclusion: </strong>These findings suggest that QUR pretreatment acts synergistically to augment the inherent anti-inflammatory and immune-regulatory properties of hUCMSCs, resulting in enhanced therapeutic efficacy for IBD treatment.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 9","pages":"105896"},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193257","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":"Exploring the critical therapeutic window: Dose-frequency optimization of human umbilical cord mesenchymal stem cells for preclinical asthma treatment.","authors":"Qiong-Hua Chen, Jing-Yang Zheng, Yu-Qin Zhu, Jun-Yao Zhang, Chun-Yan Lin, Xue-E Zhuang, Jing Cheng, Xiao-Yi Huang","doi":"10.4252/wjsc.v17.i9.109715","DOIUrl":"10.4252/wjsc.v17.i9.109715","url":null,"abstract":"<p><strong>Background: </strong>Current drugs primarily target inflammation control but do not reverse tissue remodeling changes for asthma. Human mesenchymal stem cells are known for their anti-inflammatory and tissue remodeling capabilities. However, limited research has explored the therapeutic impact of varying doses and frequencies of human umbilical cord blood-derived mesenchymal stem cells (HUC-MSCs) on established airway remodeling in experimental asthma.</p><p><strong>Aim: </strong>To explore and optimize the dosage and administration frequency of HUC-MSCs in experimental models of ovalbumin (OVA)-induced asthma.</p><p><strong>Methods: </strong>BALB/c mice underwent sensitization and were challenged using OVA. Control animals were administered a saline solution following the same protocol. HUC-MSCs were identified using flow cytometry. HUC-MSCs at incremental dosages (1 × 10⁵, 2 × 10⁵, 4 × 10⁵) were injected <i>via</i> tail veins on day 30 (the second after the final stimulation). After comparing each group and determining the optimal dose, supplement the optimal dose twice on day 30 and day 33 (the second and fifth day after the final stimulation). Bronchoalveolar lavage fluid (BALF) and serum were harvested for analysis of concentrations of interleukin-4 (IL-4), IL-13, immunoglobulin E and interferon-gamma (IFN-γ) by enzyme-linked immunosorbent assay. Pharmacology of airways and lung functions were also evaluated to identify the optimal group.</p><p><strong>Results: </strong>The study shows that HUC-MSC transplantation ameliorates OVA-induced asthma by significantly reducing airway inflammation and obstruction in preclinical models. This effect is associated with decreased Th2 cytokines IL-4 and IL-13, and increased Th1 cytokine IFN-γ. The optimal dose of 2 × 10⁵ cells/mouse was identified as the most effective in reducing local asthmatic airway inflammation and changing levels of IL-4, IL-13, and IFN-γ in serum and BALF compared to other single doses of HUC-MSC. Multiple treatments with the medium dose (2 × 10⁵ cells) of HUC-MSCs on days 30 and 33 yield the best pathological and lung function outcomes. However, double treatments do not reduce IL-4 and IL-13 expression or enhance IFN-γ production in serum or BALF more effectively than a single medium dose.</p><p><strong>Conclusion: </strong>HUC-MSCs effectively regulate pro-inflammatory mediators in serum and BALF, modulating airway remodeling and lung function. In this acute mouse asthma model, a single dosage of 2 × 10⁵ is optimal, with more significant effects of decreasing airway obstruction requiring repeated administration.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 9","pages":"109715"},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192957","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":"Combined mesenchymal and neural stem cell therapy enhances neurological recovery in cerebral infarction.","authors":"Ting Yang, Hui Yu, Dong Han, Zheng Xie","doi":"10.4252/wjsc.v17.i9.110663","DOIUrl":"10.4252/wjsc.v17.i9.110663","url":null,"abstract":"<p><strong>Background: </strong>Acute cerebral infarction (ACI), a leading cause of death and disability, causes brain ischemia due to vessel blockage. Current time-limited interventions, such as clot removal, often fail to restore full function. Neurorestoration is vital, but complicated. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) promote angiogenesis and neuroprotection. Stem cell therapy has potential to promote neurorestoration. Specifically, neural stem cells (NSC) reconstruct neural tissue, while mesenchymal stem cells (MSCs) provide support and secrete beneficial factors. Combining NSCs and MSCs in stem cell therapy may synergistically enhance ACI recovery, potentially <i>via</i> the regulation of VEGF and bFGF. However, the mechanisms underlying this combined approach remain unclear.</p><p><strong>Aim: </strong>To investigate the therapeutic effect of combined NSC and MSC transplantation on neurological recovery and bFGF/VEGF expression in ACI patients.</p><p><strong>Methods: </strong>This study enrolled 156 patients with ACI treated from June 2022 to June 2023. Patients were randomly assigned to two groups: The control group (<i>n</i> = 78) received conventional drug therapy, while the observation group (<i>n</i> = 78) received conventional therapy and combined NSC and MSC transplantation. The following outcomes were compared between groups: National Institutes of Health Stroke Scale (NIHSS) score, Barthel index, cerebral perfusion and diffusion on magnetic resonance imaging, serum bFGF and VEGF levels, clinical efficacy, and adverse events.</p><p><strong>Results: </strong>Serum VEGF and bFGF levels negatively correlated with NIHSS scores in patients with ACI (<i>r</i> = -0.388, <i>r</i> = -0.239; <i>P</i> < 0.05). The observation group (NSC and MSC) showed a significantly higher clinical efficacy of treatment than the controls (85.9% <i>vs</i> 69.2%; <i>P</i> < 0.05). Both groups showed improved cerebral perfusion, increased Barthel index, and decreased NIHSS scores post-treatment (<i>P</i> < 0.05), with significantly greater improvements in the observation group. Serum VEGF and bFGF levels increased significantly in both groups (<i>P</i> < 0.05), but were higher in the observation group. Adverse events in the observation group (transient fever: 4 cases; agitation: 1 case; headache: 2 cases) were mild and resolved with symptomatic treatment. Six-month follow-up revealed no abnormalities in magnetic resonance imaging, electrocardiogram, or blood tests.</p><p><strong>Conclusion: </strong>NSC-MSC combination therapy enhances neurological function and cerebral perfusion in patients with ACI by upregulating VEGF and bFGF expression, demonstrating favorable clinical efficacy and safety.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 9","pages":"110663"},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193289","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}