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Exercise combined with induced pluripotent stem cells enhances the Wnt1-Lmx1a loop in the midbrain of Parkinsonian mice to alleviate Parkinsonian symptoms. 运动联合诱导多能干细胞增强帕金森小鼠中脑Wnt1-Lmx1a环以减轻帕金森症状。
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-09-26 DOI: 10.4252/wjsc.v17.i9.109330
Xing Jiang, Zhi-Min Lu, Qing-Lu Wang, Ying Luo, Jie Zhang

Background: The therapeutic potential of induced pluripotent stem cells (iPSCs) for Parkinson's disease (PD) has been demonstrated. Exercise can also modulate metabolism to improve motor dysfunction in PD patients.

Aim: To investigate the therapeutic effect of exercise combined with iPSCs in a PD mouse model and explore the underlying mechanisms.

Methods: In this study, we included 10 normal mice and 40 PD model mice, which were divided into five groups: The control group (n = 10), the sedentary PD group (St group, n = 10), the exercise PD group (E group, n = 10), the iPSC-treated PD group (T group, n = 10), and the combined exercise and iPSC-treated PD group (ET group, n = 10). The T and ET groups received cell injection therapy, while the E and ET groups underwent an 8-week exercise intervention. After the intervention, behavioral tests were performed on mice from all groups. Serum levels of epinephrine (EPI) and nerve growth factor were measured, and the expression of Wnt1, Lmx1a, and other factors related to the Wnt signaling pathway in the midbrain of mice were assessed.

Results: The motor ability of the T group was higher than that of the St group, but the difference was not significant. However, the protein and gene expression levels of Wnt1, Lmx1a, Neurog2, and TH in the T group were significantly higher than those in the St group (P < 0.01). Compared with the T group, the motor ability of the E group was significantly enhanced (P < 0.01), and the gene expression level of Wnt1 in the midbrain of the E group was significantly higher than that of the T group (P < 0.05). The levels of EPI and nerve growth factor were increased in both the E and ET groups. Exercise can improve motor dysfunction in PD, increase EPI levels, and elevate Wnt1 levels. However, western blot results revealed no significant change in the TH level of the E group, which may be because exercise does not cause a noticeable change in the number of neurons. Compared with the St group, both the E and ET groups showed improved motor function (P < 0.01). The results showed that compared with the St group, the protein and gene expression levels of Wnt1, Lmx1a, and Neurog2 were significantly increased in the E, T, and ET groups (P < 0.05). Compared with the T and E groups, the protein and gene expression levels of Wnt1, Lmx1a, and Neurog2 were significantly increased in the ET group (P < 0.05).

Conclusion: Exercise increases EPI levels, activates the Wnt signaling pathway through β2 receptors, enhances the Wnt1-Lmx1a regulatory loop, and promotes the differentiation of iPSCs into dopaminergic neurons, thereby increasing the number of neurons.

背景:诱导多能干细胞(iPSCs)治疗帕金森病(PD)的潜力已经得到证实。运动还可以调节代谢,改善PD患者的运动功能障碍。目的:观察运动联合iPSCs对帕金森病小鼠模型的治疗作用,并探讨其作用机制。方法:选取正常小鼠10只,PD模型小鼠40只,分为5组:对照组(n = 10)、久坐PD组(St组,n = 10)、运动PD组(E组,n = 10)、ipsc治疗PD组(T组,n = 10)、运动与ipsc联合治疗PD组(ET组,n = 10)。T组和ET组接受细胞注射治疗,E组和ET组进行为期8周的运动干预。干预后,对各组小鼠进行行为测试。检测小鼠血清中肾上腺素(EPI)、神经生长因子水平,检测小鼠中脑中Wnt信号通路相关因子Wnt1、Lmx1a的表达。结果:T组大鼠运动能力高于St组,但差异无统计学意义。而T组Wnt1、Lmx1a、Neurog2、TH蛋白及基因表达量均显著高于St组(P < 0.01)。与T组相比,E组大鼠运动能力显著增强(P < 0.01),中脑Wnt1基因表达量显著高于T组(P < 0.05)。E组和ET组EPI和神经生长因子水平均升高。运动可以改善PD患者的运动功能障碍,提高EPI水平,提高Wnt1水平。然而,western blot结果显示,E组的TH水平没有明显变化,这可能是因为运动没有引起神经元数量的明显变化。与St组比较,E组和ET组大鼠运动功能均有改善(P < 0.01)。结果显示,与St组比较,E、T、ET组Wnt1、Lmx1a、Neurog2蛋白及基因表达量均显著升高(P < 0.05)。与T、E组比较,ET组Wnt1、Lmx1a、Neurog2蛋白及基因表达水平均显著升高(P < 0.05)。结论:运动可使EPI水平升高,通过β2受体激活Wnt信号通路,增强Wnt1-Lmx1a调控环,促进iPSCs向多巴胺能神经元分化,从而增加神经元数量。
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引用次数: 0
Human umbilical cord mesenchymal stromal cell-derived extracellular vesicles alleviate radiation induced pulmonary fibrosis. 人脐带间充质间质细胞来源的细胞外囊泡减轻辐射诱导的肺纤维化。
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-09-26 DOI: 10.4252/wjsc.v17.i9.111341
Jing-Jing Wang, Hong-Jie Xu

Pulmonary fibrosis, a chronic, fatal lung disease affecting millions worldwide, urgently needs more effective treatments. This article comments on the study by Wang et al, which proposed that human umbilical cord mesenchymal stromal cell-derived exosomes alleviate rats radiation induced pulmonary fibrosis. The study demonstrated that these exosomes suppressed inflammation, extracellular matrix deposition, and epithelial-mesenchymal transition by inhibition of AKT signaling in radiation-exposed alveolar epithelial cells. Despite these observations, aspects of the study merit further discussion. Most importantly, further confirmation is needed to prove that the therapeutic effect is exerted through the AKT signaling pathway. Moreover, the definitions of both mesenchymal stem cell and exosomes require further refinement, more rigorous terms should be mesenchymal stromal cell and extracellular vesicles. It seems apparent that this therapy will develop into one of great clinical value.

肺纤维化是一种影响全球数百万人的慢性致命肺病,迫切需要更有效的治疗方法。本文对Wang等人提出的人脐带间充质间质细胞源性外泌体减轻大鼠辐射致肺纤维化的研究进行评述。研究表明,在辐射暴露的肺泡上皮细胞中,这些外泌体通过抑制AKT信号传导抑制炎症、细胞外基质沉积和上皮间质转化。尽管有这些观察结果,该研究的某些方面值得进一步讨论。最重要的是,需要进一步证实其治疗作用是通过AKT信号通路发挥的。此外,间充质干细胞和外泌体的定义都需要进一步完善,更严格的术语应该是间充质基质细胞和细胞外囊泡。很明显,这种疗法将发展成为一种具有重大临床价值的疗法。
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引用次数: 0
Neural crest-derived mesenchymal stem cells: Fates and perspectives. 神经嵴来源的间充质干细胞:命运和前景。
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-09-26 DOI: 10.4252/wjsc.v17.i9.107689
Yi-Lin He, Si-Jia Chen, Deng-Sheng Xia, Wen-Peng Song

Neural crest-derived mesenchymal stem cells (NC-MSCs) represent a unique population with remarkable regenerative potential, owing to their embryonic origin and exceptional differentiation capacity. These cells demonstrate superior performance in neural and craniofacial tissue regeneration compared to conventional mesenchymal stem cells, with dental stem cells emerging as particularly promising candidates for clinical applications in periodontics and endodontics. Despite their therapeutic promise, adult NC-MSCs face significant challenges including donor site limitations, cellular heterogeneity, and scalability issues. Recent advances in pluripotent stem cell offer potential solutions through the generation of NC-MSCs in vitro, though safety concerns regarding tumorigenicity and long-term stability remain to be addressed through comprehensive preclinical studies. This review provides a comprehensive analysis of NC-MSC biology, highlighting their developmental origins, molecular characteristics, and current applications in regenerative medicine. We critically evaluate existing challenges and future directions, emphasizing the need for standardized protocols, improved characterization methods, and rigorous preclinical evaluation to facilitate clinical translation and therapeutic implementation.

神经嵴源性间充质干细胞(NC-MSCs)是一个独特的群体,由于其胚胎起源和特殊的分化能力,具有显著的再生潜力。与传统的间充质干细胞相比,这些细胞在神经和颅面组织再生方面表现出优越的性能,而牙干细胞在牙周病和牙髓学的临床应用中尤其有前景。尽管具有治疗前景,但成人NC-MSCs面临着巨大的挑战,包括供体部位限制、细胞异质性和可扩展性问题。多能干细胞的最新进展通过体外培养NC-MSCs提供了潜在的解决方案,尽管关于致瘤性和长期稳定性的安全性问题仍需通过全面的临床前研究来解决。本文综述了NC-MSC生物学的全面分析,重点介绍了它们的发育起源、分子特征及其在再生医学中的应用。我们批判性地评估了现有的挑战和未来的方向,强调需要标准化的协议,改进的表征方法,严格的临床前评估,以促进临床转化和治疗实施。
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引用次数: 0
HOX and MEINOX in cellular plasticity, fibrosis, and cancer. HOX和MEINOX在细胞可塑性、纤维化和癌症中的作用。
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-09-26 DOI: 10.4252/wjsc.v17.i9.109102
Mustafa Keleş, Aysen Gunel-Ozcan

HOX transcription factors and their cofactors, MEINOX, are critical regulators of positional identity and cellular plasticity. While their functions are essential during embryonic development, they also play key roles in maintaining adult tissue homeostasis. Dysregulation of HOX and MEINOX has been implicated in the pathogenesis of various diseases, including fibrosis and cancer. This review explores the contributions of HOX and MEINOX to dedifferentiation and cellular reprogramming, processes that drive fibrotic disease onset and cancer progression. It also addresses their role in extracellular matrix remodeling in these conditions. Particular attention is given to their involvement in epithelial-mesenchymal transition, where altered HOX and MEINOX expression promotes phenotypic plasticity, cancer invasiveness, and fibrotic tissue remodeling. By integrating these perspectives, this review underscores the significance of HOX-MEINOX dysregulation and altered positional identity in disease progression. Targeting this dysregulation may offer innovative strategies to modulate epithelial-mesenchymal transition and extracellular matrix dynamics, presenting new therapeutic opportunities for combating fibrosis and cancer.

HOX转录因子及其辅因子MEINOX是位置识别和细胞可塑性的关键调节因子。它们的功能在胚胎发育过程中是必不可少的,在维持成体组织稳态方面也起着关键作用。HOX和MEINOX的失调与多种疾病的发病机制有关,包括纤维化和癌症。这篇综述探讨了HOX和MEINOX在去分化和细胞重编程中的作用,这些过程驱动纤维化疾病的发生和癌症的进展。它也解决了它们在这些条件下细胞外基质重塑中的作用。特别关注它们在上皮-间质转化中的作用,其中HOX和MEINOX表达的改变促进了表型可塑性、癌症侵袭性和纤维化组织重塑。通过整合这些观点,本综述强调了HOX-MEINOX失调和位置身份改变在疾病进展中的重要性。针对这种失调可能提供创新的策略来调节上皮-间质转化和细胞外基质动力学,为对抗纤维化和癌症提供新的治疗机会。
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引用次数: 0
Advances in mesenchymal stem cell-based therapies for recurrent spontaneous abortion. 间充质干细胞治疗复发性自然流产的研究进展。
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-08-26 DOI: 10.4252/wjsc.v17.i8.108695
Yi Xiao, Fan-Yu Zeng, Zhen-Yu Chen, Feng Zhao, Jing-Li Sun

Young women's physical and mental health is seriously impacted by recurrent spontaneous abortion (RSA), a prevalent obstetric complication that is becoming more commonplace worldwide. Therefore, a thorough investigation into the pathophysiology of RSA and the development of novel therapeutic strategies are imperative. Recent developments suggest that mesenchymal stem cell (MSC)-based therapies may be viable for addressing RSA. Through a variety of mechanisms, the immunological circumstances at the maternal-fetal contact can be altered, including regulating immune cell homeostasis, enhancing immune tolerance, alleviating inflammatory responses, promoting angiogenic processes, and promoting tissue regeneration. MSCs exhibit a remarkable capacity for multi-differentiation that could enhance pregnancy outcomes. This article provides compelling studies supporting the efficacy of MSC-based therapies in improving pregnancy outcomes in women with RSA.

复发性自然流产严重影响年轻妇女的身心健康,这是一种普遍的产科并发症,在世界范围内变得越来越普遍。因此,深入研究RSA的病理生理学和发展新的治疗策略是必要的。最近的发展表明,以间充质干细胞(MSC)为基础的治疗方法可能是可行的。通过多种机制,可以改变母胎接触时的免疫环境,包括调节免疫细胞稳态,增强免疫耐受,减轻炎症反应,促进血管生成过程,促进组织再生。间充质干细胞表现出显著的多分化能力,可以提高妊娠结局。这篇文章提供了令人信服的研究,支持基于骨髓间质干细胞的治疗在改善RSA妇女妊娠结局方面的疗效。
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引用次数: 0
Advancing mechanistic insights and clinical translation of exosomal miR-137-3p in endometrial regeneration. 推进外泌体miR-137-3p在子宫内膜再生中的机制见解和临床翻译。
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-08-26 DOI: 10.4252/wjsc.v17.i8.109106
Lin-Fen Han, Guo-Kai Fu, Yue-Qi Wen, Xue-Li Bian

This study by Zhang et al elucidates the role of exosome miR-137-3p targeting ubiquitin protein ligase E3C to activate signal transducer and activator of transcription 3 under hypoxia conditions, thereby promoting the migration and differentiation of human umbilical cord mesenchymal stem cells to endometrial epithelial cells. It emphasizes that exosomal miR-137-3p/ubiquitin protein ligase E3C/signal transducer and activator of transcription 3 axis is a promising pathway for endometrial regeneration. This article introduced the therapeutic potential of exosomal microRNAs in regenerative medicine while underscoring the need for standardized protocols in optimizing exosome delivery and validating molecular pathways for clinical translation.

Zhang等的研究阐明了外泌体miR-137-3p靶向泛素蛋白连接酶E3C在缺氧条件下激活信号转导因子和转录激活因子3,从而促进人脐带间充质干细胞向子宫内膜上皮细胞的迁移和分化。强调外泌体miR-137-3p/泛素蛋白连接酶E3C/转录3轴信号换能器和激活因子是一个很有前景的子宫内膜再生途径。本文介绍了外泌体microRNAs在再生医学中的治疗潜力,同时强调了优化外泌体递送和验证临床翻译分子途径的标准化方案的必要性。
{"title":"Advancing mechanistic insights and clinical translation of exosomal miR-137-3p in endometrial regeneration.","authors":"Lin-Fen Han, Guo-Kai Fu, Yue-Qi Wen, Xue-Li Bian","doi":"10.4252/wjsc.v17.i8.109106","DOIUrl":"10.4252/wjsc.v17.i8.109106","url":null,"abstract":"<p><p>This study by Zhang <i>et al</i> elucidates the role of exosome miR-137-3p targeting ubiquitin protein ligase E3C to activate signal transducer and activator of transcription 3 under hypoxia conditions, thereby promoting the migration and differentiation of human umbilical cord mesenchymal stem cells to endometrial epithelial cells. It emphasizes that exosomal miR-137-3p/ubiquitin protein ligase E3C/signal transducer and activator of transcription 3 axis is a promising pathway for endometrial regeneration. This article introduced the therapeutic potential of exosomal microRNAs in regenerative medicine while underscoring the need for standardized protocols in optimizing exosome delivery and validating molecular pathways for clinical translation.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 8","pages":"109106"},"PeriodicalIF":3.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Roles of intestinal stem cells in inflammatory bowel disease pathogenesis. 肠道干细胞在炎症性肠病发病机制中的作用。
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-08-26 DOI: 10.4252/wjsc.v17.i8.107639
Meng-Jie Zhang, Shi-Xin Chan, Ze-Guo Jia, Chuang Lv, Jia-Jie Chen, Shao-Cheng Hong

Inflammatory bowel disease (IBD), consisting primarily of ulcerative colitis and Crohn's disease, is a chronic, relapsing inflammatory disorder of the gastrointestinal tract. The pathogenesis of IBD has been thoroughly studied throughout the past few decades, such as defective gut epithelial barrier, immune responses, genetic predisposition, infections, and dysbiosis. Recent studies have revealed the unexpected importance of intestinal stem cells (ISCs) in the pathophysiology of IBD. The rapid recovery and continuous self-renewal of intestinal epithelial cells depend on ISCs within the crypts. Proliferation and differentiation of ISCs is an important cytological basis for repairing damaged intestinal mucosa. Unfortunately, as a new therapeutic goal in IBD, mucosal healing is difficult to achieve with current treatments. Stem cell therapy is an emerging treatment for IBD that allows mucosal healing by rebuilding the mucosal barrier. In this review, we present the current research progress on the role of ISCs in IBD and discuss stem cell-based therapies that have been specifically designed for its treatment.

炎症性肠病(IBD)是一种慢性、复发性胃肠道炎症性疾病,主要由溃疡性结肠炎和克罗恩病组成。在过去的几十年里,人们对IBD的发病机制进行了深入的研究,如肠道上皮屏障缺陷、免疫反应、遗传易感性、感染和生态失调。最近的研究揭示了肠干细胞(ISCs)在IBD病理生理中的意想不到的重要性。肠上皮细胞的快速恢复和持续自我更新依赖于隐窝内的ISCs。ISCs的增殖分化是修复肠黏膜损伤的重要细胞学基础。不幸的是,作为IBD的一个新的治疗目标,黏膜愈合在目前的治疗方法中很难实现。干细胞疗法是一种新兴的IBD治疗方法,通过重建粘膜屏障使粘膜愈合。在这篇综述中,我们介绍了目前关于ISCs在IBD中的作用的研究进展,并讨论了专门为IBD治疗设计的基于干细胞的治疗方法。
{"title":"Roles of intestinal stem cells in inflammatory bowel disease pathogenesis.","authors":"Meng-Jie Zhang, Shi-Xin Chan, Ze-Guo Jia, Chuang Lv, Jia-Jie Chen, Shao-Cheng Hong","doi":"10.4252/wjsc.v17.i8.107639","DOIUrl":"10.4252/wjsc.v17.i8.107639","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), consisting primarily of ulcerative colitis and Crohn's disease, is a chronic, relapsing inflammatory disorder of the gastrointestinal tract. The pathogenesis of IBD has been thoroughly studied throughout the past few decades, such as defective gut epithelial barrier, immune responses, genetic predisposition, infections, and dysbiosis. Recent studies have revealed the unexpected importance of intestinal stem cells (ISCs) in the pathophysiology of IBD. The rapid recovery and continuous self-renewal of intestinal epithelial cells depend on ISCs within the crypts. Proliferation and differentiation of ISCs is an important cytological basis for repairing damaged intestinal mucosa. Unfortunately, as a new therapeutic goal in IBD, mucosal healing is difficult to achieve with current treatments. Stem cell therapy is an emerging treatment for IBD that allows mucosal healing by rebuilding the mucosal barrier. In this review, we present the current research progress on the role of ISCs in IBD and discuss stem cell-based therapies that have been specifically designed for its treatment.</p>","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 8","pages":"107639"},"PeriodicalIF":3.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Applications of artificial intelligence in stem cell therapy. 人工智能在干细胞治疗中的应用。
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-08-26 DOI: 10.4252/wjsc.v17.i8.106086
Mahmood S Choudhery, Taqdees Arif, Ruhma Mahmood

Stem cell therapy holds great promise for the regeneration and repair of damaged tissues and organs. Stem cell therapy has been successfully applied to treat diseases that cannot be cured with conventional medicine. A careful evaluation of the outcomes is required for successful implementation of stem cell therapy. Recently, artificial intelligence (AI) has opened new avenues for research in the stem cell therapy field. The integration of AI can assist in evaluating the quality, efficiency and safety of stem cells by analyzing available data. It has the potential to improve and accelerate progress in various aspects of stem cell research and therapeutic applications. AI is still in its infancy and has certain limitations, such as algorithm validation problems, inadequate data availability, poor data quality, and ethical considerations. Considering the potential of AI to improve stem cell research and therapeutics, this review aims to explore applications of AI in understanding stem cell behavior, identification and characterization, optimization of the delivery methods, stem cell modeling and prediction of mortality risk. In addition, this review highlights the role of AI, machine learning, deep learning, and other subtypes in advancing stem cell biology research. This review also discusses the current limitations, ethical considerations, and future prospective of use of AI in stem cell research and therapeutic applications.

干细胞疗法对受损组织和器官的再生和修复有着巨大的希望。干细胞疗法已经成功地应用于治疗传统医学无法治愈的疾病。成功实施干细胞治疗需要对结果进行仔细的评估。最近,人工智能(AI)为干细胞治疗领域的研究开辟了新的途径。人工智能的整合可以通过分析现有数据来帮助评估干细胞的质量、效率和安全性。它有可能改善和加速干细胞研究和治疗应用的各个方面的进展。人工智能仍处于起步阶段,存在一定的局限性,如算法验证问题、数据可用性不足、数据质量差、伦理考虑等。考虑到人工智能在干细胞研究和治疗方面的潜力,本文旨在探讨人工智能在理解干细胞行为、鉴定和表征、递送方法优化、干细胞建模和死亡风险预测方面的应用。此外,本综述还强调了人工智能、机器学习、深度学习和其他亚型在推进干细胞生物学研究中的作用。这篇综述还讨论了目前人工智能在干细胞研究和治疗应用中的局限性、伦理考虑和未来前景。
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引用次数: 0
Expression of stem cell marker musashi-1 and its relationship with survival prognosis in patients with resectable esophageal squamous cell carcinoma. 可切除食管鳞状细胞癌患者干细胞标志物musashi-1的表达及其与生存预后的关系
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-08-26 DOI: 10.4252/wjsc.v17.i8.107013
Ya-Xuan Niu, Min Hu, Wei-Feng Zhao, Hong-Jie Yang
<p><strong>Background: </strong>Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors globally, with its incidence particularly high in East Asia.</p><p><strong>Aim: </strong>To analyze the expression of the stem cell marker musashi-1 in patients with resectable ESCC undergoing neoadjuvant chemotherapy and its relationship with patient survival prognosis.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on the clinical data of 74 ESCC patients treated at our hospital from June 2020 to January 2022. All patients received neoadjuvant chemotherapy and surgical resection. Immunohistochemistry (IHC) was used to detect musashi-1 expression in tumor tissues. Based on the expression intensity, patients were divided into group A (<i>n</i> = 30, IHC total score > 2 indicating high expression) and group B (<i>n</i> = 44, IHC total score 0-2 indicating low expression). The clinical pathological differences between groups A and B were compared. The treatment outcomes of both groups were compared. Univariate and multivariate Cox regression analysis was performed to identify factors affecting patient prognosis. Kaplan-Meier survival analysis was used, and log-rank tests were conducted to compare differences between groups.</p><p><strong>Results: </strong>There were statistically significant differences in tumor maximum diameter, T stage, N stage, clinical stage, pathological grade, lymphovascular invasion, and intraoperative blood loss between groups A and B (<i>P</i> < 0.05). The disease control rate in group A (86.67%) was lower than that in group B (100.00%) (<i>χ</i> <sup>2</sup> = 3.868, <i>P</i> = 0.049); the objective response rate in group A (33.33%) was lower than that in group B (70.45%) (<i>χ</i> <sup>2</sup> = 9.948, <i>P</i> = 0.001). The proportion of tumor regression grade 3 + 4 + 5 grades in group A (80.00%) was higher than in group B (43.18%) (<i>χ</i> <sup>2</sup> = 9.933, <i>P</i> = 0.001). Univariate analysis showed that tumor maximum diameter, T stage, N stage, clinical stage, pathological grade, and musashi-1 expression were associated with patient prognosis (<i>P</i> < 0.05). Cox regression analysis model. The results indicated that T stage [hazard ratio (HR) = 1.82, 95% confidence interval (CI): 2.14-7.37], N stage (HR = 1.70, 95%CI: 1.12-2.36), clinical stage (HR = 2.08, 95%CI: 1.36-3.85), pathological grade (HR = 1.54, 95%CI: 1.07-2.41), and musashi-1 expression (HR = 2.72, 95%CI: 2.03-4.11) were independent risk factors affecting patient prognosis (<i>P</i> < 0.05). Kaplan-Meier survival curves showed that the median overall survival in group A was 17 months, while in group B it was 28 months. Log-rank analysis revealed that the overall survival rate in group A was worse than in group B (<i>χ</i> <sup>2</sup> = 2.635, <i>P</i> = 0.033).</p><p><strong>Conclusion: </strong>The expression of musashi-1 is closely related to the treatment efficacy, prognosis, and survival of ESCC patient
背景:食管鳞状细胞癌(ESCC)是全球最常见的恶性肿瘤之一,在东亚地区发病率特别高。目的:分析干细胞标志物musashi-1在可切除ESCC患者新辅助化疗中的表达及其与患者生存预后的关系。方法:回顾性分析我院2020年6月至2022年1月收治的74例ESCC患者的临床资料。所有患者均接受新辅助化疗和手术切除。免疫组化(IHC)检测肿瘤组织中musashi-1的表达。根据表达强度将患者分为A组(n = 30, IHC总分bb0 2,高表达)和B组(n = 44, IHC总分0-2,低表达)。比较A组与B组临床病理差异。比较两组患者的治疗效果。采用单因素和多因素Cox回归分析确定影响患者预后的因素。采用Kaplan-Meier生存分析,采用log-rank检验比较组间差异。结果:A组与B组在肿瘤最大直径、T分期、N分期、临床分期、病理分级、淋巴血管侵犯、术中出血量等指标上比较,差异均有统计学意义(P < 0.05)。A组疾病控制率(86.67%)低于B组(100.00%)(χ 2 = 3.868, P = 0.049);客观有效率A组(33.33%)低于B组(70.45%)(χ 2 = 9.948, P = 0.001)。A组肿瘤消退3 + 4 + 5级比例(80.00%)高于B组(43.18%)(χ 2 = 9.933, P = 0.001)。单因素分析显示,肿瘤最大直径、T分期、N分期、临床分期、病理分级、musashi-1表达与患者预后相关(P < 0.05)。Cox回归分析模型。结果显示,T分期[危险比(HR) = 1.82, 95%可信区间(CI): 2.14 ~ 7.37]、N分期(HR = 1.70, 95%CI: 1.12 ~ 2.36)、临床分期(HR = 2.08, 95%CI: 1.36 ~ 3.85)、病理分级(HR = 1.54, 95%CI: 1.07 ~ 2.41)、musashi-1表达(HR = 2.72, 95%CI: 2.03 ~ 4.11)是影响患者预后的独立危险因素(P < 0.05)。Kaplan-Meier生存曲线显示,A组中位总生存期为17个月,B组中位总生存期为28个月。Log-rank分析显示,A组总生存率低于B组(χ 2 = 2.635, P = 0.033)。结论:musashi-1的表达与ESCC患者的治疗效果、预后及生存密切相关。它有望成为评估ESCC患者疗效和生存预后的潜在生物标志物。
{"title":"Expression of stem cell marker musashi-1 and its relationship with survival prognosis in patients with resectable esophageal squamous cell carcinoma.","authors":"Ya-Xuan Niu, Min Hu, Wei-Feng Zhao, Hong-Jie Yang","doi":"10.4252/wjsc.v17.i8.107013","DOIUrl":"10.4252/wjsc.v17.i8.107013","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors globally, with its incidence particularly high in East Asia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;To analyze the expression of the stem cell marker musashi-1 in patients with resectable ESCC undergoing neoadjuvant chemotherapy and its relationship with patient survival prognosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A retrospective analysis was conducted on the clinical data of 74 ESCC patients treated at our hospital from June 2020 to January 2022. All patients received neoadjuvant chemotherapy and surgical resection. Immunohistochemistry (IHC) was used to detect musashi-1 expression in tumor tissues. Based on the expression intensity, patients were divided into group A (&lt;i&gt;n&lt;/i&gt; = 30, IHC total score &gt; 2 indicating high expression) and group B (&lt;i&gt;n&lt;/i&gt; = 44, IHC total score 0-2 indicating low expression). The clinical pathological differences between groups A and B were compared. The treatment outcomes of both groups were compared. Univariate and multivariate Cox regression analysis was performed to identify factors affecting patient prognosis. Kaplan-Meier survival analysis was used, and log-rank tests were conducted to compare differences between groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;There were statistically significant differences in tumor maximum diameter, T stage, N stage, clinical stage, pathological grade, lymphovascular invasion, and intraoperative blood loss between groups A and B (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). The disease control rate in group A (86.67%) was lower than that in group B (100.00%) (&lt;i&gt;χ&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; = 3.868, &lt;i&gt;P&lt;/i&gt; = 0.049); the objective response rate in group A (33.33%) was lower than that in group B (70.45%) (&lt;i&gt;χ&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; = 9.948, &lt;i&gt;P&lt;/i&gt; = 0.001). The proportion of tumor regression grade 3 + 4 + 5 grades in group A (80.00%) was higher than in group B (43.18%) (&lt;i&gt;χ&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; = 9.933, &lt;i&gt;P&lt;/i&gt; = 0.001). Univariate analysis showed that tumor maximum diameter, T stage, N stage, clinical stage, pathological grade, and musashi-1 expression were associated with patient prognosis (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Cox regression analysis model. The results indicated that T stage [hazard ratio (HR) = 1.82, 95% confidence interval (CI): 2.14-7.37], N stage (HR = 1.70, 95%CI: 1.12-2.36), clinical stage (HR = 2.08, 95%CI: 1.36-3.85), pathological grade (HR = 1.54, 95%CI: 1.07-2.41), and musashi-1 expression (HR = 2.72, 95%CI: 2.03-4.11) were independent risk factors affecting patient prognosis (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Kaplan-Meier survival curves showed that the median overall survival in group A was 17 months, while in group B it was 28 months. Log-rank analysis revealed that the overall survival rate in group A was worse than in group B (&lt;i&gt;χ&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; = 2.635, &lt;i&gt;P&lt;/i&gt; = 0.033).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The expression of musashi-1 is closely related to the treatment efficacy, prognosis, and survival of ESCC patient","PeriodicalId":23775,"journal":{"name":"World journal of stem cells","volume":"17 8","pages":"107013"},"PeriodicalIF":3.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Aligned nanofiber scaffolds combined with cyclic stretch facilitate mesenchymal stem cell differentiation for ligament engineering. 排列纳米纤维支架复合循环拉伸促进韧带工程间充质干细胞分化。
IF 3.6 3区 医学 Q3 CELL & TISSUE ENGINEERING Pub Date : 2025-08-26 DOI: 10.4252/wjsc.v17.i8.107124
Cheng-Wei Yang, Ya-Qiang Zhang, Hong Chang, Rui Gao, Dan Chen, Hao Yao
<p><strong>Background: </strong>Tendon tissue engineering requires biomimetic scaffolds and mechanical cues to direct mesenchymal stem cell differentiation toward tenogenic lineages. Bone marrow-derived mesenchymal stem cells (BMSCs), aligned nanofiber scaffolds, and cyclic uniaxial stretching can be used to create a functional engineered ligament tissue.</p><p><strong>Aim: </strong>To investigate the effects of aligned nanofiber scaffolds and cyclic stretch on BMSC tenogenesis for ligament engineering.</p><p><strong>Methods: </strong>BMSCs were cultured on aligned and random poly-lactic acid nanofiber scaffolds under static and cyclic tensile conditions (0.5 Hz, 2% strain, 2 hours/day) for 7 days using a mechanical loading system (CFILLOAD-300). The Ras homolog gene family (Rho)-associated coiled coil-containing kinase (ROCK) inhibitor Y27632 was applied to explore its role in tenogenic differentiation. Scaffold morphology was assessed by scanning electron microscopy, while cell morphology, viability, and alignment were evaluated <i>via</i> confocal microscopy with F-actin and 4',6-diamidino-2-phenylindole staining. Tenogenic gene expression (collagen type I alpha 2, collagen type III alpha 1, tenascin C, and tenomodulin) was quantified by quantitative polymerase chain reaction, and ligament-related protein levels (collagen I, collagen III, tenascin C, and tenomodulin) were analyzed by western blot.</p><p><strong>Results: </strong>Scanning electron microscopy revealed that aligned scaffolds provided consistent directional structure, whereas random scaffolds displayed a disordered fiber arrangement. Confocal microscopy showed that under static conditions, BMSCs on aligned scaffolds grew parallel to fiber alignment, while those on random scaffolds grew randomly. Under cyclic tensile strain, BMSCs on both scaffold types exhibited elongation along the direction of strain, adopting a spindle-shaped morphology. Cyclic uniaxial strain enhanced cell viability and metabolic activity based on CCK-8 assay results and upregulated ligament-specific gene and protein expression on aligned scaffolds compared to static conditions. BMSCs on aligned scaffolds under tensile strain showed the highest expression of tenogenic markers, suggesting a synergistic effect of scaffold alignment and mechanical loading. ROCK inhibition with Y27632 upregulated alternative signaling pathways (focal adhesion kinase and runt-related transcription factor 2), further promoting tenogenic differentiation.</p><p><strong>Conclusion: </strong>Aligned nanofiber scaffolds combined with cyclic tensile strain provide an optimal environment for guiding BMSC differentiation toward ligamentous lineages, as assessed by increased expression of ligament-specific markers. Mechanical stimulation (uniaxial stretching) significantly influences BMSC tenogenic differentiation, and the combined use of aligned nanofibers and tensile strain further enhances this effect. The ROCK pathway plays a regulatory
背景:肌腱组织工程需要仿生支架和机械线索来引导间充质干细胞向肌腱系分化。骨髓间充质干细胞(BMSCs)、排列纳米纤维支架和循环单轴拉伸可用于创建功能性工程韧带组织。目的:探讨排列纳米纤维支架和循环拉伸对韧带工程中骨髓间充质干细胞肌腱生成的影响。方法:采用机械加载系统(CFILLOAD-300),在静态和循环拉伸条件下(0.5 Hz, 2%应变,2小时/天),在排列和随机聚乳酸纳米纤维支架上培养BMSCs 7天。应用Ras同源基因家族(Rho)相关的coil-containing kinase (ROCK)抑制剂Y27632探讨其在肌腱分化中的作用。通过扫描电镜评估支架形态,通过F-actin共聚焦显微镜和4',6-二氨基-2-苯基吲哚染色评估细胞形态、活力和排列。采用定量聚合酶链式反应定量测定致腱基因表达(I型胶原α 2、III型胶原α 1、tenascin C、tenomodulin), western blot分析韧带相关蛋白水平(I型胶原、III型胶原、tenascin C、tenomodulin)。结果:扫描电镜显示,排列支架具有一致的定向结构,而随机支架则显示出无序的纤维排列。共聚焦显微镜显示,在静态条件下,排列支架上的骨髓间充质干细胞生长方向与纤维排列平行,而随机支架上的骨髓间充质干细胞生长方向是随机的。在循环拉伸应变作用下,两种支架上的骨髓间充质干细胞沿应变方向均表现出伸长,呈纺锤状形态。基于CCK-8检测结果,与静态条件相比,循环单轴应变增强了细胞活力和代谢活性,并且在排列支架上上调了韧带特异性基因和蛋白质的表达。在拉伸应变作用下,排列支架上的骨髓间充质干细胞的成肌腱标记物表达最高,表明支架排列和机械载荷具有协同作用。Y27632抑制ROCK可上调其他信号通路(局灶黏附激酶和矮子相关转录因子2),进一步促进肌腱分化。结论:排列纳米纤维支架结合循环拉伸应变为引导BMSC向韧带谱系分化提供了最佳环境,可通过增加韧带特异性标记物的表达来评估。机械刺激(单轴拉伸)显著影响骨髓间充质干细胞的成肌腱分化,而排列纳米纤维和拉伸应变的联合使用进一步增强了这种影响。ROCK通路在这一过程中发挥调控作用,但其确切机制有待进一步研究。
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World journal of stem cells
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