International journal of stem cells最新文献

{"title":"Evaluation of Pyrene Induced Cardiotoxicity Using Dual-Cardiotoxicity Evaluation Method.","authors":"Hyewon Shin, C-Yoon Kim, Hyung Min Chung, Seul-Gi Lee","doi":"10.15283/ijsc25108","DOIUrl":"10.15283/ijsc25108","url":null,"abstract":"<p><p>Pyrene (Pyr), a representative subtype of polycyclic aromatic hydrocarbons, is primarily generated during the incomplete combustion of organic matter. As an environmental pollutant, Pyr has been reported to exert adverse effects on various physiological systems. However, data regarding its cardiotoxicity remain limited. In this study, we investigated the acute cardiotoxic effects of Pyr using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). hiPSC-CMs were exposed to various doses of Pyr, and both cell viability and functional parameters were evaluated. Pyr did not affect cell viability under 30-minute and 2-hour exposure conditions regardless of dose. However, significant differences were observed in the dual-cardiotoxicity evaluation based on a microelectrode array, which allows simultaneous assessment of electrophysiological signals and contractility in CMs. Pyr decreased beat period and field potential duration in a dose-dependent manner, resembling the acute cardiotoxicity pattern of IKr and ICaL channel blockers, and progressively reduced spike amplitude over time. Although a transient decrease in beat amplitude was observed at high dose, it recovered over time, while the excitation-contraction delay was reduced. Taken together, these findings demonstrate that Pyr can induce functional cardiotoxicity even under acute exposure and highlight the value of the established evaluation method for the development of safer alternative substances.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"331-345"},"PeriodicalIF":2.6,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of a Patient-Derived Inducible Pluripotent Stem Cell Model for Studying the <i>YARS2</i>-Related Genetic Disease.","authors":"Chenbo Zeng, Andrew Gray, Rebecca Ganetzky, Ya-Ming Hou, Lorraine Iacovitti","doi":"10.15283/ijsc25101","DOIUrl":"10.15283/ijsc25101","url":null,"abstract":"<p><p>The <i>YARS2</i> variant, harboring the compound heterozygous pathogenic mutations F185L/E264del, was identified in the gene for mitochondrial tyrosyl-tRNA synthetase in a proband that suffered a neonatal phenotype. To facilitate studies to better understand the severity of the mutations, we created a patient-derived inducible pluripotent stem cell (iPSC) model. We first derived iPSCs from fibroblasts of the patient Q1818, which contain two mutations, c.553T> C (p.F185L) and c.792_794delAGA (p.E264del) in the <i>YARS2</i> gene. We then generated three isogenic control iPSC lines with one or both mutations corrected by using CRISPR-Cas9 technology. The correction of mutations in <i>YARS2</i> was confirmed by Sanger sequencing. The stemness of iPSC lines was demonstrated by the expression of stem cell markers in the iPSCs, as determined using qPCR, immunostaining, and trilineage differentiation. Moreover, three positive clones of each iPSC line were extensively characterized, confirming that they originated from Q1818 fibroblasts, had normal karyotypes, and did not contain off-targets in the <i>YARS2</i> coding sequence; genome wide off target effects were not a major concern. Subsequently, Q1818 iPSCs and the three isogenic control iPSCs were differentiated into clinically relevant motor neurons. In addition, we demonstrated that the patient fibroblasts and the derived iPSCs are heterozygous for either c. 553T>C or c.792_794delAGA, and that the two mutations are located on different alleles of the <i>YARS2</i> gene, providing critical information for studying the mutation-associated disease. In conclusion, we have generated a set of four iPSC lines, which can be used as a model to study a clinically severe case of <i>YARS2</i> disease.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"360-369"},"PeriodicalIF":2.6,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Genetically Engineered Mouse Models of Melanoma: Insights into Tumor Initiation and Oncogenic Signaling Pathways.","authors":"Hyeonji Choi, Jung Hyun Lee, Hye Ji Cha, Yoonho Shin, Sekyu Choi","doi":"10.15283/ijsc25131","DOIUrl":"10.15283/ijsc25131","url":null,"abstract":"<p><p>Genetically engineered mouse (GEM) models are essential for elucidating the cellular and molecular mechanisms underlying various human diseases. Because mouse skin closely resembles the structure and lineage organization of human skin, melanoma GEM models enable the investigation of melanoma initiation in melanocytes and melanocyte stem cells, along with its progression from the epidermis to the dermis. Although early melanoma development is mainly regulated by major oncogenic signaling pathways, including MAPK and PI3K, recent studies have uncovered additional regulatory pathways, including Cdk4-mediated cell-cycle control, Jak-Stat-mediated transcriptional regulation, Hippo-Yap/Taz signaling, the p62-Igf2bp1 axis, and epigenetic regulators such as Tet2, which contribute to melanoma heterogeneity and phenotypic plasticity. This review summarizes the recent advances in melanoma GEM models, highlights the oncogenic signaling pathways active in these systems, and discusses the molecular insights derived from these models regarding melanoma initiation, progression, and intratumoral diversity. These findings highlight the utility of GEM models for elucidating melanoma biology and identifying potential therapeutic targets.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"294-307"},"PeriodicalIF":2.6,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Notice to: Improvement of Human Sperm Vacuolization and DNA Fragmentation Co-Cultured with Adipose-Derived Mesenchymal Stem Cell Secretome: <i>In Vitro</i> Effect.","authors":"Robert Bader, José-Noel Ibrahim, Ali Mourad, Mayssam Moussa, Joan Azoury, Joseph Azoury, Nada Alaaeddine","doi":"10.15283/ijsc19047R","DOIUrl":"10.15283/ijsc19047R","url":null,"abstract":"","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":"19 3","pages":"378"},"PeriodicalIF":2.6,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"cP1P Maintains Long-Term Pluripotency in Human Pluripotent Stem Cells.","authors":"Sang Hyeon Woo, Sehyun Chae, Byung-Ho Rhie, Won-Jun Jo, Young Jun Park, Myeong-Jun Choi, Viswanathaiah Matam, Suresh Ramakrishna, Daehee Hwang, Kye-Seong Kim","doi":"10.15283/ijsc25107","DOIUrl":"10.15283/ijsc25107","url":null,"abstract":"<p><p>Long-term culture of human pluripotent stem cells (hPSCs) can lead to spontaneous mutations, genomic abnormalities, and alterations in gene expression, thereby compromising their self-renewal and pluripotency. Thus, optimizing the long-term culture conditions of hPSCs is crucial. In this study, we introduce O-cyclic phytosphingosine-1-phosphate (cP1P, Axceso Biopharma Co. Ltd.), a novel culture additive structurally analogous to S1P, which markedly enhances hPSC self-renewal and survival. Our results demonstrate that cP1P supplementation promotes long-term proliferation of hPSCs by upregulating pluripotency markers and maintaining their ability to differentiate into cell types derived from the three germ layers. Furthermore, RNA-seq analysis reveals that cP1P alleviates long-term culture-induced upregulation of apoptosis- and chordate embryonic development-related genes, while preventing the downregulation of stem cell maintenance pathways. Collectively, these findings suggest that cP1P effectively supports the proliferation, pluripotency, and differentiation potential of hPSCs during both short- and long-term cultures.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"320-330"},"PeriodicalIF":2.6,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147929616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Preliminary Study on Evaluating Reparative Regeneration Potential of Human Amniotic Fluid Stem Cells Spheres in Stress Urinary Incontinence Rats.","authors":"Shing-Hwa Lu, Shiaw-Min Hwang, Navneet Kumar Dubey, Ming-Song Tsai, Tien-Fu Yun, Jiunn-Wang Liao","doi":"10.15283/ijsc25121","DOIUrl":"10.15283/ijsc25121","url":null,"abstract":"<p><p>Recent reports indicate that stem cell spheres might offer enhanced therapeutic benefits by promoting cell engraftment ability, stemness, angiogenesis, and chemotaxis. Hence, we investigated whether amniotic fluid stem cells (AFSC) spheres could provide therapeutic benefits in stress urinary incontinence (SUI) due to their urethral sphincter-specific commitment. The isolated human AFSCs were characterized by flow-cytometry-based immunophenotyping and their multidifferentiation potential (osteo-, adipo-, and chondrogenic lineages). Time-dependent (>12, 16∼20, and 48 hours) culture conditions for AFSCsphere formation were optimized. Urodynamic parameters, including leak point pressure (LPP) and intercontraction interval (ICI), were determined. hAFSCsphere with ∼150 <i>μ</i>m diameter with minimal core necrosis at 16∼20 hours was found optimal for therapeutic application in the pudendal nerve injury-induced SUI rat model. The AFSCs demonstrated mesenchymal stem cell characteristics and multi-differentiation capabilities with retained levels of pluripotency and neural progenitor markers, SOX2 and nestin, respectively. Compared to AFSC, the AFSCsphere group showed superior LPP and ICI in rats; however, with either modest, relatively low, or unchanged levels of myogenic-lineage genes (<i>myf</i>5, myoD, myogenin, and desmin) between them. Bladder and external urethral sphincter histologic architecture were also improved. Notably, AFSCsphere showed the elevated levels of secretome (VEGF, IL-6, IL-8, IL-9, and MIP-1<i>β</i>) than AFSC, when compared to control. This could be attributed to non-myogenic pathways, such as paracrine dominance, including anti-inflammatory, angiogenic, or neurotrophic. Conclusively, our study revealed that AFSCsphere may improve urodynamics despite a significant increase in myogenic regulatory factor expression. Therefore, future studies should quantify AFSCsphere-specific properties, like stemness and cell-cell interactions, in reaching enhanced therapeutic outcomes.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"346-359"},"PeriodicalIF":2.6,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148411739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CXCL14 Enhances Myocyte Fusion and Activates the FAK-ERK5 Signaling Pathway in Skeletal Muscle Stem Cells and Myoblasts.","authors":"Nurkyz Alymkulova, Younjeong Oh, Jennifer Fransisca, Bagus Sarmito, Yongsung Hwang, Jeong Kyo Yoon","doi":"10.15283/ijsc26042","DOIUrl":"10.15283/ijsc26042","url":null,"abstract":"<p><p>Skeletal muscle regeneration is essential for maintaining muscle function throughout life and is regulated by numerous growth factors, cytokines and their associated signaling pathways. In this study, we investigated the role of C-X-C motif chemokine ligand 14 (CXCL14) in myogenic differentiation using skeletal muscle stem cells (MuSC) and the mouse myoblast C2C12 cell line. Notably, CXCL14 significantly enhanced myocyte fusion. To elucidate the underlying regulatory mechanisms, we examined fusion-associated signaling pathways and found that CXCL14 activates the focal adhesion kinase-extracellular regulated protein kinase 5 (FAK-ERK5) signaling pathway. Our findings identify the CXCL14-FAK-ERK5 signaling axis as a positive regulator of myocyte fusion. Furthermore, by establishing fibro-adipogenic progenitors (FAPs) as the primary source of CXCL14 and demonstrating its pro-fusion activity, this study provides new insight into the paracrine regulation from FAPs to MuSCs during muscle regeneration.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"370-377"},"PeriodicalIF":2.6,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lineage-Driven Understanding of Human Pericyte Heterogeneity in Vascular Modeling and Regeneration.","authors":"Seungyeon Lee, Chan Mi Baek, Somin Lee, Min Gi Jo, Yong Jun Kim","doi":"10.15283/ijsc26028","DOIUrl":"10.15283/ijsc26028","url":null,"abstract":"<p><p>Pericytes are mural cells embedded within the microvascular wall that regulate endothelial stabilization, angiogenesis, and vascular permeability. Once regarded as a relatively uniform vascular support population, pericytes are now recognized as quantitatively and functionally heterogeneous across organs. Neural barrier beds such as brain and retina exhibit high pericyte density and near-continuous mural coverage, whereas peripheral tissues including skeletal muscle display sparse investment. These anatomical differences parallel functional specialization, with central nervous system pericytes exerting strong control over blood-brain barrier (BBB) integrity and transcytosis, while peripheral pericytes participate prominently in vascular remodeling and repair. A critical yet under-integrated dimension of this heterogeneity is developmental origin. Trunk and visceral pericytes arise predominantly from mesodermal progenitors, whereas cranial and forebrain-associated pericytes derive largely from neural crest lineage. This spatial segregation of embryonic origin aligns with vascular specialization, suggesting that lineage contributes to mural regulatory architecture. Stem cell-based comparisons further demonstrate that neural crest-derived pericyte-like cells induce BBB phenotypes more effectively than mesoderm-derived counterparts under identical endothelial conditions, supporting a lineage-linked functional bias. This review integrates anatomical distribution, quantitative investment patterns, molecular signaling mechanisms, and embryonic lineage into a unified framework of pericyte heterogeneity. We propose that developmental origin establishes a regulatory foundation upon which vascular niche signals act, and should therefore be treated as a primary experimental and translational design variable in vascular modeling and regenerative strategies.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"273-293"},"PeriodicalIF":2.6,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascularized Brain Organoids: Advances in Engineering Human Neurovascular Models.","authors":"Hee Young Kim, Jung Eun Lee, Seung Ho Yang, Jai Ho Choi","doi":"10.15283/ijsc25139","DOIUrl":"10.15283/ijsc25139","url":null,"abstract":"<p><p>Brain organoids have emerged as an important platform for studying human neurodevelopment and neurological disorders, yet their physiological relevance remains limited by the absence of a functional vascular network. Recent efforts therefore focus on developing vascularized brain organoids (vBOs) to better recapitulate neurovascular interactions. Here, we investigate current strategies for vBO engineering, discussing its potential implications such as disease modeling, drug screening, and regenerative therapies along with persistent challenges in reproducing physiologically mature neurovascular features. This review outlines a rapidly evolving framework that enhances neurovascular modeling and supports emerging translational research in neurological disorders.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"257-272"},"PeriodicalIF":2.6,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148446677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Cerebral Organoid Model of Familial Alzheimer's Disease Using Amyloid Precursor Protein Mutation, Val669Leu (<i>APP^Seoul</i>).","authors":"Won Hee Jung, Seung Tack Oh, Mu Seog Choe, Yu Jin Kwon, So Jin Kim, Ye Seong Jeon, Kyung Min Baek, Woochul Chang, Kyung Seob Lim, Joong Sun Kim, Seung Pil Yun, Min Young Lee","doi":"10.15283/ijsc25044","DOIUrl":"10.15283/ijsc25044","url":null,"abstract":"<p><p>Various animal and cellular Alzheimer's disease (AD) models harboring familial AD (fAD) mutations have been developed and widely used for AD research. In this study, we established an AD cerebral organoid (CO) model using a novel Val669Leu (<i>APP</i>^<i>Seoul</i>) mutation in the APP gene. We generated a human embryonic stem cell (hESC) line overexpressing <i>APP</i>^<i>Seoul</i>, referred to as the fAD-S hESC line. Using this line, we produced COs and confirmed robust AD-associated pathologies, including amyloid-<i>β</i> (A<i>β</i>) accumulation and tau phosphorylation. In addition, increased expression of <i>β</i>-secretase was observed in this model. Based on these findings, we investigated the effects of BACE1 inhibitor IV, a <i>β</i>-secretase inhibitor, in the CO model. Treatment with BACE1 inhibitor IV significantly reduced A<i>β</i> levels and tau phosphorylation. Furthermore, we differentiated the fAD-S hESC line into cortical neurons (fAD-S neurons) to establish a 2D cellular AD model. Consistent with the CO results, fAD-S neurons exhibited elevated levels of A<i>β</i> and phosphorylated tau, which were also significantly attenuated by BACE1 inhibitor IV treatment. Collectively, these results demonstrate the successful establishment of hESC-derived 2D and 3D AD models based on the <i>APP</i>^<i>Seoul</i> fAD mutation.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":"308-319"},"PeriodicalIF":2.6,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148603183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}