International journal of stem cells最新文献

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Advanced Animal Replacement Testing Strategies Using Stem Cell and Organoids. 使用干细胞和类器官的先进动物替代试验策略。
IF 2.5 4区 医学
International journal of stem cells Pub Date : 2025-05-30 Epub Date: 2025-03-11 DOI: 10.15283/ijsc24118
Chang-Jin Lee, Yoojun Nam, Yeri Alice Rim, Ji Hyeon Ju
{"title":"Advanced Animal Replacement Testing Strategies Using Stem Cell and Organoids.","authors":"Chang-Jin Lee, Yoojun Nam, Yeri Alice Rim, Ji Hyeon Ju","doi":"10.15283/ijsc24118","DOIUrl":"10.15283/ijsc24118","url":null,"abstract":"<p><p>The increasing ethical concerns and regulatory restrictions surrounding animal testing have accelerated the development of advanced in vitro models that more accurately replicate human physiology. Among these, stem cell-based systems and organoids have emerged as revolutionary tools, providing ethical, scalable, and physiologically relevant alternatives. This review explores the key trends and driving factors behind the adoption of these models, such as technological advancements, the principles of the 3Rs (Replacement, Reduction, and Refinement), and growing regulatory support from agencies like the OECD and FDA. It also delves into the development and application of various model systems, including 3D reconstructed tissues, induced pluripotent stem cell-derived cells, and microphysiological systems, highlighting their potential to replace animal models in toxicity evaluation, disease modeling, and drug development. A critical aspect of implementing these models is ensuring robust quality control protocols to enhance reproducibility and standardization, which is necessary for gaining regulatory acceptance. Additionally, we discuss advanced strategies for assessing toxicity and efficacy, focusing on organ-specific evaluation methods and applications in diverse fields such as pharmaceuticals, cosmetics, and food safety. Despite existing challenges related to scalability, standardization, and regulatory alignment, these innovative models represent a transformative step towards reducing animal use and improving the relevance and reliability of preclinical testing outcomes.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"107-125"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Collagen Scaffold Augments the Therapeutic Effect of Human Umbilical Cord Mesenchymal Stem Cells in a Rat Model of Intrauterine Adhesion. 胶原支架增强人脐带间充质干细胞对大鼠宫内粘连模型的治疗作用。
IF 2.5 4区 医学
International journal of stem cells Pub Date : 2025-05-30 Epub Date: 2025-02-25 DOI: 10.15283/ijsc24079
Linzhi Gao, Guifang Jiang, Enming Liang, Ying Zhang, Baoling Cheng, Xian Zhang, Dong Zhang, Xiaoyu Wang, Yuan Shen
{"title":"Collagen Scaffold Augments the Therapeutic Effect of Human Umbilical Cord Mesenchymal Stem Cells in a Rat Model of Intrauterine Adhesion.","authors":"Linzhi Gao, Guifang Jiang, Enming Liang, Ying Zhang, Baoling Cheng, Xian Zhang, Dong Zhang, Xiaoyu Wang, Yuan Shen","doi":"10.15283/ijsc24079","DOIUrl":"10.15283/ijsc24079","url":null,"abstract":"<p><p>Intrauterine adhesion (IUA) caused by endometrial injury is the most common cause of female uterine infertility. Current treatments offer limited clinical benefits. In this study, we investigated the role of human umbilical cord mesenchymal stem cells (hUCMSCs) loaded collagen scaffold in the regeneration of injured human endometrium in an IUA rat model. Following the construction of the IUA rat model by mechanical injury, collagen scaffold, hUCMSCs, or hUCMSCs-loaded collagen scaffold was transplanted. The implantation of hUCMSCs-loaded collagen scaffold significantly increased the thickness of the endometrium, the number of endometrial glands and the abundance of blood vessels in IUA rats. Moreover, hUCMSCs-loaded collagen scaffold treatment significantly reduced endometrial fibrosis, increased the expression of <i>Vegf, Integrin β3, Lif</i>, and <i>Igf-1</i>, and finally improved endometrial receptivity in IUA rats. Taken together, our observations suggest that hUCMSCs-loaded collagen scaffold could be a practical therapeutic for treating IUA and restoring regeneration.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"135-145"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mammalian Blastema: Possibility and Potentials. 哺乳动物胚芽:可能性和潜力。
IF 2.5 4区 医学
International journal of stem cells Pub Date : 2025-05-30 Epub Date: 2025-03-10 DOI: 10.15283/ijsc24121
Juhyeon Nam, Byungkuk Min, Areum Baek, Sang-Yun Lee, Jeongmin Ha, Min Ji Cho, Janghwan Kim
{"title":"Mammalian Blastema: Possibility and Potentials.","authors":"Juhyeon Nam, Byungkuk Min, Areum Baek, Sang-Yun Lee, Jeongmin Ha, Min Ji Cho, Janghwan Kim","doi":"10.15283/ijsc24121","DOIUrl":"10.15283/ijsc24121","url":null,"abstract":"<p><p>Regeneration is a process that restores the structure and function of injured tissues or organs. Regenerative capacities vary significantly across species, with amphibians and fish demonstrating a high regenerative capacity even after severe injuries. This capacity is largely attributed to the formation of a blastema, a mass of multipotent cells reprogrammed from differentiated cells at the injury site. In contrast, mammals exhibit limited regenerative capacities, with blastema- like cells forming only in specific contexts, such as antler or digit tip regeneration. An interesting aspect of blastema formation in highly regenerative organisms is the temporary expression of pluripotency factors as known as the Yamanaka factors (YFs), which is a key requirement for reprogramming somatic cells into induced pluripotent stem cells (iPSCs). While iPSCs hold pros and cons, direct or partial reprogramming with YF has been proposed as a safer alternative. Since blastema formation and partial reprogramming are similar in terms of YF expressions, we found blastema-like cells in mammalian reprogramming with YF. This review outlines the characteristics of blastema across various organisms, emphasizing interspecies differences. We also explore studies on partial reprogramming and the possibility of inducing blastema-like cells via the temporary expression of YF in mammals.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"126-134"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Loss of Ubiquitin-Specific Protease 11 Mitigates Pulmonary Fibrosis in Human Pluripotent Stem Cell-Derived Alveolar Organoids. 泛素特异性蛋白酶11的缺失减轻了人多能干细胞衍生肺泡类器官的肺纤维化。
IF 2.5 4区 医学
International journal of stem cells Pub Date : 2025-05-30 Epub Date: 2025-04-07 DOI: 10.15283/ijsc25011
Sripriya Rajkumar, Ji-Hye Jung, Ji-Young Kim, Janardhan Keshav Karapurkar, Girish Birappa, D A Ayush Gowda, C Bindu Ajaykumar, Haribalan Perumalsamy, Bharathi Suresh, Kye-Seong Kim, Seok-Ho Hong, Suresh Ramakrishna
{"title":"Loss of Ubiquitin-Specific Protease 11 Mitigates Pulmonary Fibrosis in Human Pluripotent Stem Cell-Derived Alveolar Organoids.","authors":"Sripriya Rajkumar, Ji-Hye Jung, Ji-Young Kim, Janardhan Keshav Karapurkar, Girish Birappa, D A Ayush Gowda, C Bindu Ajaykumar, Haribalan Perumalsamy, Bharathi Suresh, Kye-Seong Kim, Seok-Ho Hong, Suresh Ramakrishna","doi":"10.15283/ijsc25011","DOIUrl":"10.15283/ijsc25011","url":null,"abstract":"<p><p>The etiology of chronic and lethal interstitial lung disease, termed idiopathic pulmonary fibrosis (IPF), remains unidentified. IPF induces pathological lung scarring that results in rigidity and impairs gas exchange, eventually resulting in premature mortality. Recent findings indicate that deubiquitinating enzymes play a key role in stabilizing fibrotic proteins and contribute to pulmonary fibrosis. The ubiquitin-specific protease 11 (USP11) promotes pro-fibrotic proteins, and its expression elevated in tissue samples from patients with IPF. Thus, this study aimed to examine the effects of loss of function of <i>USP11</i> gene on the progression of pulmonary fibrosis by utilizing 3D cell culture alveolar organoids (AOs) that replicate the structure and functions of the proximal and distal airways and alveoli. Here, we applied the CRISPR/Cas9 system to knock out the <i>USP11</i> gene in human induced pluripotent stem cells (hiPSCs) and then differentiated these hiPSCs into AOs. Loss of <i>USP11</i> gene resulted in abnormalities in type 2 alveolar epithelial cells in the hiPSC-USP11KO-AOs. Moreover, knock out of the <i>USP11</i> mitigates pulmonary fibrosis caused by TGF-<i>β</i> in hiPSC-USP11KO-AOs by reducing collagen formation and fibrotic markers, suggesting it has the therapeutic potential to treat IPF patients.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"205-213"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of Dexamethasone and Tacrolimus on Mesenchymal Stem Cell Characteristics and Gene Expression. 地塞米松和他克莫司对间质干细胞特性和基因表达的影响
IF 2.5 4区 医学
International journal of stem cells Pub Date : 2025-05-30 Epub Date: 2025-03-14 DOI: 10.15283/ijsc24116
Na Kyung Lee, Duk L Na, Su Hyeon Myeong, Seung-Yeon Lee, Na-Hee Lee, Hyemin Jang, Sang Won Seo, Jong Wook Chang, Hee Jin Kim, Hyo Jin Son
{"title":"Effects of Dexamethasone and Tacrolimus on Mesenchymal Stem Cell Characteristics and Gene Expression.","authors":"Na Kyung Lee, Duk L Na, Su Hyeon Myeong, Seung-Yeon Lee, Na-Hee Lee, Hyemin Jang, Sang Won Seo, Jong Wook Chang, Hee Jin Kim, Hyo Jin Son","doi":"10.15283/ijsc24116","DOIUrl":"10.15283/ijsc24116","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are frequently used for therapeutic applications in both pre-clinical and clinical settings owing to their capacity for immune modulation and neuroprotective effects. However, transient fever is commonly observed as an adverse event following MSC injection in patients with Alzheimer's disease (AD). In this study, we investigated the potential impact of immunosuppressants such as dexamethasone and tacrolimus on altering the characteristics of human mesenchymal stem cells (hMSCs). Additionally, we examined whether these immunosuppressants affect the persistence of hMSCs or the immune response upon their administration into the brain parenchyma of AD mice. The exposure of hMSCs to high concentrations of dexamethasone and tacrolimus <i>in vitro</i> did not significantly alter the characteristics of hMSCs. The expression of genes related to innate immune responses, such as <i>Irak1, Irf3, Nod1</i>, and <i>Ifnar1</i>, was significantly downregulated by the additional administration of dexamethasone and tacrolimus to the brain parenchyma of AD mice. However, hMSC persistence in the AD mouse brain was not affected. The results of this study support the use of immunosuppressants to mitigate fever during stem cell therapy in patients with AD.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"173-185"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PML Regulated HIF1AN Ubiquitination and Activated PI3K/AKT Pathway to Promote Bone Marrow Mesenchymal Stem Cells Osteogenic Differentiation. PML调节HIF1AN泛素化,激活PI3K/AKT通路促进骨髓间充质干细胞成骨分化。
IF 2.5 4区 医学
International journal of stem cells Pub Date : 2025-05-30 Epub Date: 2025-03-10 DOI: 10.15283/ijsc24110
Xian-Pei Zhou, Qi-Wei Li, Zi-Zhen Shu, Yang Liu
{"title":"PML Regulated HIF1AN Ubiquitination and Activated PI3K/AKT Pathway to Promote Bone Marrow Mesenchymal Stem Cells Osteogenic Differentiation.","authors":"Xian-Pei Zhou, Qi-Wei Li, Zi-Zhen Shu, Yang Liu","doi":"10.15283/ijsc24110","DOIUrl":"10.15283/ijsc24110","url":null,"abstract":"<p><p>Osteoporosis (OP) is a metabolic disease caused by osteogenesis and bone resorption disorders. Promyelocytic leukemia protein (PML) was a vital regulator of cellular functions. However, the function of PML in OP remains unknown. Our research aimed to illustrate the molecular mechanism of PML in bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation. The BMSCs were identified by using flow cytometry analysis. The osteoblast differentiation ability of BMSCs was assessed through using alkaline phosphatase and Alizarin red S stainings. The relationship between hypoxia-inducible factor-1<i>α</i> (HIF1<i>α</i>) and superoxide dismutase 3 (SOD3) were confirmed by using chromatin immunoprecipitation and dual-luciferase reporter assays. The binding association between PML and hypoxia-inducible factor 1<i>α</i> inhibitor (HIF1AN) proteins was verified by using co-immunoprecipitation assay and immunofluorescence staining. Western blot was used for protein detection. PML was up-regulated in osteogenic differentiation of BMSCs. Functionally, PML negatively regulated HIF1AN expression by enhancing HIF1AN ubiquitination degradation. PML knockdown or HIF1AN up-regulation suppressed the osteogenic differentiation of BMSCs. Furthermore, HIF1<i>α</i> directly bound to the SOD3 promoter region. PML or SOD3 overexpression remarkably promoted the BMSCs osteoblast differentiation under osteogenic medium, which was reversed by LY294002. PML acts as a significant regulator in the BMSCs osteogenic differentiation by regulating the HIF1AN/HIF1<i>α</i>/SOD3 axis and phosphatidylinositol 3 kinase/protein kinase B pathway.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"146-157"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Application of Deep Neural Networks in the Manufacturing Process of Mesenchymal Stem Cells Therapeutics. 深度神经网络在间充质干细胞疗法制造过程中的应用。
IF 2.5 4区 医学
International journal of stem cells Pub Date : 2025-05-30 Epub Date: 2024-09-26 DOI: 10.15283/ijsc24070
Dat Ngo, Jeongmin Lee, Sun Jae Kwon, Jin Hun Park, Baek Hwan Cho, Jong Wook Chang
{"title":"Application of Deep Neural Networks in the Manufacturing Process of Mesenchymal Stem Cells Therapeutics.","authors":"Dat Ngo, Jeongmin Lee, Sun Jae Kwon, Jin Hun Park, Baek Hwan Cho, Jong Wook Chang","doi":"10.15283/ijsc24070","DOIUrl":"10.15283/ijsc24070","url":null,"abstract":"<p><p>Current image-based analysis methods for monitoring cell confluency and status depend on individual interpretations, which can lead to wide variations in the quality of cell therapeutics. To overcome these limitations, images of mesenchymal stem cells cultured adherently in various types of culture vessels were captured and analyzed using a deep neural network. Among the various deep learning methods, a classification and detection algorithm was selected to verify cell confluency and status. We confirmed that the image classification algorithm demonstrates significant accuracy for both single- and multistack images. Abnormal cells could be detected exclusively in single-stack images, as multistack culture was performed only when abnormal cells were absent in the single-stack culture. This study is the first to analyze cell images based on a deep learning method that directly impacts yield and quality, which are important product parameters in stem cell therapeutics.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"186-193"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mesenchymal Stem Cells Mediated Suppression of GREM2 Inhibits Renal Epithelial-Mesenchymal Transition and Attenuates the Progression of Diabetic Kidney Disease. 间充质干细胞介导的GREM2抑制肾上皮-间充质转化并减缓糖尿病肾病的进展
IF 2.5 4区 医学
International journal of stem cells Pub Date : 2025-05-30 Epub Date: 2025-01-06 DOI: 10.15283/ijsc24113
Myoung Seok Ko, Ji-Young Yun, Serin Kim, Mi-Ok Kim, Sang-Hyeok Go, Hye Jin Jin, Eun Hee Koh
{"title":"Mesenchymal Stem Cells Mediated Suppression of GREM2 Inhibits Renal Epithelial-Mesenchymal Transition and Attenuates the Progression of Diabetic Kidney Disease.","authors":"Myoung Seok Ko, Ji-Young Yun, Serin Kim, Mi-Ok Kim, Sang-Hyeok Go, Hye Jin Jin, Eun Hee Koh","doi":"10.15283/ijsc24113","DOIUrl":"10.15283/ijsc24113","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. Despite advancements in various treatments, the prevalence of DKD continues to rise, leading to a significant increase in the demand for dialysis and kidney transplantation. This study aimed to evaluate the effects of a Small cell+Ultra Potent+Scale UP cell (SMUP-Cell), a type of human umbilical cord blood-derived mesenchymal stem cell, on DKD in the db/db mouse model of type 2 diabetes mellitus. After administering SMUP-Cells via tail vein injection in db/db mice, the animals were monitored over a three-month period. The <i>db/db</i> mice exhibited an increased urine albumin-to-creatinine ratio (UACR). However, the administration of SMUP-Cells resulted in a reduction of the UACR. The expression levels of desmin, α-smooth muscle actin, and fibronectin-markers of epithelial-mesenchymal transition (EMT)-as well as kidney injury molecule 1, a sensitive marker of tubular injury, were significantly elevated in <i>db/db</i> mice. Treatment with SMUP-Cells ameliorated all of these changes. Notably, Gremlin isoform 2 (<i>Grem2</i>) exhibited the most significant difference in expression according to the transcriptome analysis. The elevated expression of <i>Grem2</i> in <i>db/db</i> mice was significantly reduced following SMUP-Cell treatment. In vitro, treatment with high glucose and cholesterol induced <i>Grem2</i> expression in renal tubular epithelial cells (RTECs), while <i>Grem2</i> knockdown effectively prevented fibrosis and senescence induced by high glucose and cholesterol in RTECs. These observations suggest that SMUP-Cells inhibit the progression of DKD by inhibiting EMT through the reduction of <i>Grem2</i> expression in RTECs.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"158-172"},"PeriodicalIF":2.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Functional Validation of Alcohol Dependence-Associated FYN Variants Using Gene Editing and Stem Cell Study Approaches. 使用基因编辑和干细胞研究方法对酒精依赖相关FYN变异的功能验证
IF 2.5 4区 医学
International journal of stem cells Pub Date : 2025-04-10 DOI: 10.15283/ijsc24123
Bilal Cakir, Yoshiaki Tanaka, Mu Seog Choe, Pei-Yu Chu, Yangfei Xiang, Kun-Yong Kim, Mei Zhong, Joel Gelernter, Huiping Zhang, John Krystal, In-Hyun Park
{"title":"Functional Validation of Alcohol Dependence-Associated <i>FYN</i> Variants Using Gene Editing and Stem Cell Study Approaches.","authors":"Bilal Cakir, Yoshiaki Tanaka, Mu Seog Choe, Pei-Yu Chu, Yangfei Xiang, Kun-Yong Kim, Mei Zhong, Joel Gelernter, Huiping Zhang, John Krystal, In-Hyun Park","doi":"10.15283/ijsc24123","DOIUrl":"https://doi.org/10.15283/ijsc24123","url":null,"abstract":"<p><p>Alcohol dependence (AD) is one of the most prevalent neuropsychiatric disorders. Multiple polymorphisms in the Fyn tyrosine kinase gene (<i>FYN</i>) were found to be associated with AD. The function of AD-associated <i>FYN</i> variants remains largely unknown due to the absence of an appropriate model for studying them. Here, we generated human embryonic stem cell lines homozygous/heterozygous for rs706895 C/T alleles in 5' untranslated region (5' UTR) of <i>FYN</i> by CRISPR-Cas9 editing to explore the AD association. Transcriptome and reporter gene analyses demonstrated that induced neurons with the rs706895 C allele showed a significantly higher expression level of <i>FYN</i> under ethanol treatment. Our results suggest that <i>FYN</i> 5' UTR variant rs706895 may influence an individual's vulnerability to AD by altering <i>FYN</i> expression. Targeting AD-associated variants may provide a better understanding of disease mechanisms and a reliable basis for the personalized AD treatment.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Phase 1/2a Clinical Trial to Evaluate the Efficacy and Safety of Allogenic Adipose Tissue-Derived Mesenchymal Stem Cell Clusters in Patients with Critical Limb Ischemia. 一项评估同种异体脂肪组织来源的间充质干细胞簇在重度肢体缺血患者中的有效性和安全性的1/2a期临床试验
IF 2.5 4区 医学
International journal of stem cells Pub Date : 2025-03-17 DOI: 10.15283/ijsc25002
Yong-Man Park, Joon-Kee Park, Hyo-Shin Kim, Shin-Seok Yang, Jong-Wan Kim, Dong-Ik Kim
{"title":"A Phase 1/2a Clinical Trial to Evaluate the Efficacy and Safety of Allogenic Adipose Tissue-Derived Mesenchymal Stem Cell Clusters in Patients with Critical Limb Ischemia.","authors":"Yong-Man Park, Joon-Kee Park, Hyo-Shin Kim, Shin-Seok Yang, Jong-Wan Kim, Dong-Ik Kim","doi":"10.15283/ijsc25002","DOIUrl":"https://doi.org/10.15283/ijsc25002","url":null,"abstract":"<p><p>Critical limb ischemia (CLI) is a severe manifestation of peripheral arterial disease, often resulting in ischemic rest pain, non-healing ulcers, or gangrene. Due to the limited effectiveness of conventional revascularization techniques in 5%∼20% of patients, alternative therapeutic approaches are needed. This Phase 1/2a clinical trial evaluated the safety, tolerability, and efficacy of allogeneic adipose tissue-derived mesenchymal stem cell clusters (ADMSCCs) in patients with CLI who were not eligible for standard revascularization methods. The study was conducted in two phases: Phase 1 used a 3+3 dose-escalation design to determine tolerability, and Phase 2a assessed efficacy at the maximum tolerated dose. Twenty patients were treated with ADMSCCs, with safety (adverse events and dose-limiting toxicity) and efficacy (pain intensity, walking distance, and ulcer size) as primary endpoints. ADMSCCs were injected intramuscularly, and patients were monitored for 24 weeks. ADMSCCs were well-tolerated, with no serious adverse events or dose-limiting toxicities observed. Significant reductions in ischemic pain and increases in pain-free walking distance were noted at 4, 12, and 24 weeks. Although ankle-brachial index and toe-brachial index showed no significant changes, ulcer healing was observed in one participant. These findings suggest that ADMSCC therapy may be a viable alternative for patients with CLI, with a favorable safety profile and sustained therapeutic effects. Further studies with larger sample sizes and randomized control groups are needed to confirm these results and explore integration with existing treatments.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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