International journal of stem cells最新文献

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Vascularized Brain Organoids: Advances in Engineering Human Neurovascular Models. 血管化脑类器官:工程人类神经血管模型的进展。
IF 2.6 4区 医学
International journal of stem cells Pub Date : 2026-08-30 Epub Date: 2026-07-15 DOI: 10.15283/ijsc25139
Hee Young Kim, Jung Eun Lee, Seung Ho Yang, Jai Ho Choi
{"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}
引用次数: 0
A Cerebral Organoid Model of Familial Alzheimer's Disease Using Amyloid Precursor Protein Mutation, Val669Leu (APPSeoul). 利用淀粉样蛋白前体蛋白突变Val669Leu建立家族性阿尔茨海默病脑类器官模型
IF 2.6 4区 医学
International journal of stem cells Pub Date : 2026-08-30 Epub Date: 2026-07-29 DOI: 10.15283/ijsc25044
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
{"title":"A Cerebral Organoid Model of Familial Alzheimer's Disease Using Amyloid Precursor Protein Mutation, Val669Leu (<i>APP<sup>Seoul</sup></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><sup><i>Seoul</i></sup>) mutation in the APP gene. We generated a human embryonic stem cell (hESC) line overexpressing <i>APP</i><sup><i>Seoul</i></sup>, 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><sup><i>Seoul</i></sup> 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}
引用次数: 0
Optimization of a Canine Colon Organoid Platform for Modeling Intestinal Injury and Mesenchymal Stem Cell-Mediated Regeneration. 犬结肠类器官模拟肠道损伤和间充质干细胞介导的再生平台的优化。
IF 2.6 4区 医学
International journal of stem cells Pub Date : 2026-08-25 DOI: 10.15283/ijsc26011
Hee-Jeong Park, Hyeon Seo Lee, Yunji Lee, Jeong Hyun Yu, Ji-Won Yang, Ji-Su Ahn, Eui-Suk Sung, Min Jang, Yoojin Seo, Hyung-Sik Kim
{"title":"Optimization of a Canine Colon Organoid Platform for Modeling Intestinal Injury and Mesenchymal Stem Cell-Mediated Regeneration.","authors":"Hee-Jeong Park, Hyeon Seo Lee, Yunji Lee, Jeong Hyun Yu, Ji-Won Yang, Ji-Su Ahn, Eui-Suk Sung, Min Jang, Yoojin Seo, Hyung-Sik Kim","doi":"10.15283/ijsc26011","DOIUrl":"https://doi.org/10.15283/ijsc26011","url":null,"abstract":"<p><p>Canine chronic enteropathy (CE) is characterized by persistent mucosal inflammation and impaired barrier function. Despite its high clinical prevalence, research has been hindered by a lack of host-specific intestinal models. Here, we present an optimized canine-derived colon organoid (cCO) culture platform designed for assessing drug toxicity and regenerative potential. Combining Wnt/EGF activation with TGF-β/p38 MAPK inhibition supported the long-term maintenance of stem cell-enriched organoids. Upon maturation, differentiated cCOs exhibited both absorptive and secretory cells, validated by lineage-specific marker expression and functional P-glycoprotein efflux activity. While pro-inflammatory cytokines exerted non-specific toxicity, diclofenac-induced injury was significantly more pronounced in differentiated organoids than in expanding counterparts. This indicates that our platform effectively recapitulates the cell type-specific sensitivity of the intestinal epithelium to pharmacological insults. Next, to determine whether the cCOs could model epithelial repair process, we examined the therapeutic effects of canine mesenchymal stem cells (MSCs), a representative cell-based therapy for CE, on damaged organoids. Notably, treatment with MSC-conditioned media (MSC-CM) triggered a morphological transition into cystic spheroids with the upregulation of pro-regenerative stem cell markers, suggesting the induction of a fetal-like regenerative reprogramming. Indeed, MSC-CM treatment restored growth and proliferation while preserving barrier integrity in diclofenac-treated organoids. Collectively, these findings demonstrate the advantages of cCO system for modeling intestinal injury and repair, supporting the development of targeted therapeutic strategies for canine gastrointestinal disorders.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813007","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
Efficacy and Safety of Low-Molecular-Weight Collagen Peptide GT for Improving Hair Condition in Individuals with Damaged Hair: A Randomized, Double-Blind, Placebo-Controlled Trial. 低分子胶原肽GT改善受损发质的有效性和安全性:一项随机、双盲、安慰剂对照试验
IF 2.6 4区 医学
International journal of stem cells Pub Date : 2026-08-21 DOI: 10.15283/ijsc26035
Taek-Kyong Kim, Jintaek Oh, Yoon-Su Ha, Hee-Ju Son, Joon Sung Yang, Kyungseok Kim, Young Her, Seung-Kyoon Kim, Seonghwan Hwang, Se-Ran Yang, Jaewoo Choi, Seung-Jin Kim
{"title":"Efficacy and Safety of Low-Molecular-Weight Collagen Peptide GT for Improving Hair Condition in Individuals with Damaged Hair: A Randomized, Double-Blind, Placebo-Controlled Trial.","authors":"Taek-Kyong Kim, Jintaek Oh, Yoon-Su Ha, Hee-Ju Son, Joon Sung Yang, Kyungseok Kim, Young Her, Seung-Kyoon Kim, Seonghwan Hwang, Se-Ran Yang, Jaewoo Choi, Seung-Jin Kim","doi":"10.15283/ijsc26035","DOIUrl":"10.15283/ijsc26035","url":null,"abstract":"<p><p>Addressing hair damage is essential for maintaining overall hair and scalp health. Previous studies have suggested that low-molecular-weight collagen peptides may support hair follicle biology through regulation of extracellular matrix homeostasis and cellular signaling pathways. In addition, recent preclinical studies have demonstrated that low-molecular-weight fish collagen peptides promote hair regrowth through activation of proliferative signaling and suppression of inhibitory pathways. However, their clinical efficacy in improving hair damage has not been clearly established. In this study, the efficacy and safety of low-molecular-weight collagen peptide GT (LMWCP GT) were evaluated in Korean adults with damaged hair. In a randomized, placebo-controlled trial, individuals aged 19∼60 years without alopecia but with mild to moderate hair damage received LMWCP GT (3 g/day) for 24 weeks. Compared with placebo, the treatment group demonstrated significant improvements in hair gloss, as measured using a gloss meter (SAMBA) and scanning electron microscopy, as well as in hair elasticity, assessed by tensile strength and hair diameter. Subjective evaluations further indicated improvements in overall hair condition, including gloss, elasticity, thickness, texture, fullness, and appearance. In addition, scalp elasticity was significantly increased in the treatment group. No treatment-related adverse events were observed. These findings indicate that daily supplementation with LMWCP GT (3 g/day) for 24 weeks is safe and effective in improving overall hair condition in individuals with damaged hair without alopecia.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792994","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
Therapeutic Effect of Pioglitazone-Pretreated Human Wharton's Jelly-Derived Mesenchymal Stem Cells in a Rat Tendon Injury Model. 吡格列酮预处理人类沃顿氏凝胶源间充质干细胞对大鼠肌腱损伤模型的治疗作用。
IF 2.6 4区 医学
International journal of stem cells Pub Date : 2026-08-21 DOI: 10.15283/ijsc26036
Won Kim, Soo Kim, Seul Ki Lee, Young-Won Kwon, Sun G Chung
{"title":"Therapeutic Effect of Pioglitazone-Pretreated Human Wharton's Jelly-Derived Mesenchymal Stem Cells in a Rat Tendon Injury Model.","authors":"Won Kim, Soo Kim, Seul Ki Lee, Young-Won Kwon, Sun G Chung","doi":"10.15283/ijsc26036","DOIUrl":"https://doi.org/10.15283/ijsc26036","url":null,"abstract":"<p><p>The clinical application of mesenchymal stem cells (MSCs) has several limitations owing to their less therapeutic efficacy. Effect enhancement and MSCs from new sources might help in overcoming these limitations. The aim of the present study was to investigate the therapeutic effects of human Wharton's jelly-derived MSCs (hWJMSCs) and pioglitazone-pretreated MSCs (Pio-MSCs) in a rat tendon injury model. Fifty-four Sprague Dawley rats were randomly assigned to three groups: phosphate-buffered saline (PBS) group, implanted with PBS; MSC group, implanted with MSCs; and Pio-MSC group, implanted with Pio-MSCs. The cell or PBS with fibrin glue mixture was implanted around bilateral window defect in the Achilles tendons of the rats. The cross-sectional area measurement, histological analysis, gene expression, protein expression, and biomechanical analysis were performed at 2 and 4 weeks after modeling. Pio-MSC group revealed a significantly higher gene expression level of <i>Col3</i> than PBS group at 2 weeks and that of <i>TnC</i> at 2 and 4 weeks. Moreover, MSC group revealed significantly higher gene expression level of <i>Col1</i> than PBS group at 2 weeks. In general, the expression levels of <i>Col1, Col3, Scx,</i> and <i>TnC</i> were the highest in Pio-MSC group, followed by MSC and PBS groups. Furthermore, Pio-MSC group revealed significantly higher tenascin C-stained fraction than PBS group at 4 weeks. These findings suggest a potential role of hWJMSCs in tendon regeneration; however, the <i>in vivo</i> enhancement effect of pioglitazone pretreatment over MSC alone was not confirmed, and no differences were observed in histological or biomechanical outcomes among the groups.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793001","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
Human-Relevant Microphysiological Systems: Evidence for Defined Contexts of Use. 与人类相关的微生理系统:定义使用环境的证据。
IF 2.6 4区 医学
International journal of stem cells Pub Date : 2026-08-20 DOI: 10.15283/ijsc26088
Minseo Byeon, Eunseo Park, Jihoon Ko
{"title":"Human-Relevant Microphysiological Systems: Evidence for Defined Contexts of Use.","authors":"Minseo Byeon, Eunseo Park, Jihoon Ko","doi":"10.15283/ijsc26088","DOIUrl":"https://doi.org/10.15283/ijsc26088","url":null,"abstract":"<p><p>The FDA Modernization Act has accelerated the transition from animal-based testing toward human-relevant new approach methodologies in drug development, shifting attention from technological feasibility to regulatory implementation. Among these approaches, microphysiological systems (MPS) can generate evidence that more directly reflects human physiology, but their regulatory readiness varies substantially across applications. This Review summarizes recent regulatory developments and evaluates the readiness of major organ-specific and multi-organ MPS. Liver MPS have advanced furthest through quantitative benchmarking, industrial adoption and sustained regulatory engagement, whereas kidney, lung, gastrointestinal, tumor, nervous system and multi-organ models remain limited by varying degrees of standardization, independent validation and clearly defined regulatory use. Across applications, major barriers include insufficiently specified contexts of use, limited human benchmark data, inadequate multicenter reproducibility, manufacturing variability and fragmented data infrastructure. We discuss priorities for overcoming these barriers, including performance-based standards, quality-controlled manufacturing, auditable data systems and earlier coordination among technology developers, end users and regulatory authorities. Patient-derived and stem cell-derived models, artificial intelligence and digital twins may further extend the scope of MPS, but their value will depend on transparent validation and integration with complementary evidence. Regulatory adoption is likely to proceed incrementally, with MPS initially supporting defined decisions as complementary evidence and replacing conventional studies when their performance and uncertainty are sufficiently characterized.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148792955","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
Fibroblast Growth Factor Signaling in Lung Diseases: From Biological Roles to Therapeutic Delivery Strategies. 肺疾病中的成纤维细胞生长因子信号:从生物学作用到治疗递送策略。
IF 2.6 4区 医学
International journal of stem cells Pub Date : 2026-08-07 DOI: 10.15283/ijsc26054
Se Bi Lee, Young Her, Dae-Hee Lee, Se-Ran Yang
{"title":"Fibroblast Growth Factor Signaling in Lung Diseases: From Biological Roles to Therapeutic Delivery Strategies.","authors":"Se Bi Lee, Young Her, Dae-Hee Lee, Se-Ran Yang","doi":"10.15283/ijsc26054","DOIUrl":"https://doi.org/10.15283/ijsc26054","url":null,"abstract":"<p><p>As human longevity continues to increase globally, the prevalence of age-related deterioration and associated chronic lung diseases has risen in parallel. Unlike many organs, the lung is continuously exposed to environmental insults, leading to cumulative cellular damage, impaired epithelial progenitor activity, and chronic inflammation, which contribute to diseases such as pulmonary fibrosis and chronic obstructive pulmonary disease. Under physiological conditions, lung homeostasis is maintained by epithelial progenitor cells, particularly alveolar type II cells. However, this regenerative capacity is often disrupted in chronic lung diseases, resulting in impaired repair and fibrotic remodeling. Fibroblast growth factors (FGFs) and their receptors (FGFRs) play critical roles in epithelial regeneration, cell survival, and tissue repair. Despite their therapeutic potential, clinical translation remains limited by poor protein stability, rapid proteolytic degradation, low delivery efficiency across biological barriers, and insufficient cell-type specificity due to broad FGFR expression. Recently, several delivery strategies have been evaluated in preclinical lung disease models, including protein engineering, nanoparticle and liposome-based platforms, protein transduction domain- and cell-penetrating peptide-based intracellular delivery, and mesenchymal stem cell-based approaches. Therefore, this review summarizes the roles of FGF signaling in lung regeneration and age-associated diseases, and discusses emerging delivery strategies aimed at bridging the gap between preclinical efficacy and clinical application.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684533","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
Genome-Wide Characterization of Recombinant AAV6 Vector Integration in Human CD34+ Cells. 重组AAV6载体在人CD34+细胞中整合的全基因组特性
IF 2.6 4区 医学
International journal of stem cells Pub Date : 2026-07-27 DOI: 10.15283/ijsc26038
Hyeon Jeong Lee, Nayoung Park, In-Byung Park, Seok-Jin Kang, Joonbeom Bae, Jaebum Kim, Taehoon Chun
{"title":"Genome-Wide Characterization of Recombinant AAV6 Vector Integration in Human CD34<sup>+</sup> Cells.","authors":"Hyeon Jeong Lee, Nayoung Park, In-Byung Park, Seok-Jin Kang, Joonbeom Bae, Jaebum Kim, Taehoon Chun","doi":"10.15283/ijsc26038","DOIUrl":"https://doi.org/10.15283/ijsc26038","url":null,"abstract":"<p><p>Several viral vectors have been developed for gene therapy due to their high transduction efficiency, but some integrate into the host genome, raising safety concerns. Recent studies have identified recombinant adeno-associated virus serotype 6 (rAAV6) as a promising vector for hematopoietic stem and progenitor cell-targeted gene therapy because of its non-pathogenic nature, low integration frequency, and capacity for sustained episomal transgene expression. Nevertheless, its chromosomal integration profile remains incompletely defined, warranting a comprehensive evaluation to assess long-term safety. In this study, human CD34<sup>+</sup> cells were transduced with rAAV6 under varying vector doses and transgene contexts, and integration-site mapping was performed using the integration-site enriched library sequencing approach. Consistent with the largely episomal nature of AAV, high vector sequence alignment rates were observed across all groups. rAAV6 integrations occurred randomly throughout the genome, showing a broad pan-chromosomal distribution without evidence of sequence-specific targeting or clustering. Although integrations were more frequent in CpG islands, commonly located within open chromatin, this pattern likely reflects chromatin accessibility rather than targeting bias. Functional enrichment analysis indicated associations with general cellular and structural processes, without enrichment in oncogenic pathways. Distance-based analysis confirmed that integration sites were mapped at a distance from oncogenes and tumor suppressor genes, even under high-dose conditions. The data support the genomic safety of rAAV6 and its applicability to hematological gene therapy.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591741","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
Adipose-Derived Mesenchymal Stem Cells Improve Motor Function and Reduce Neuroinflammation and Mutant Ataxin-3 Protein Levels in SCA3 Mice. 脂肪来源的间充质干细胞改善SCA3小鼠的运动功能,减少神经炎症和Ataxin-3突变蛋白水平。
IF 2.6 4区 医学
International journal of stem cells Pub Date : 2026-07-02 DOI: 10.15283/ijsc25141
Kuan-Ming Lu, Wei-Kee Ong, ChingHuai Ko, Ling-Mei Wang, Anthony E Ting, Hsiu-Yu Lai
{"title":"Adipose-Derived Mesenchymal Stem Cells Improve Motor Function and Reduce Neuroinflammation and Mutant Ataxin-3 Protein Levels in SCA3 Mice.","authors":"Kuan-Ming Lu, Wei-Kee Ong, ChingHuai Ko, Ling-Mei Wang, Anthony E Ting, Hsiu-Yu Lai","doi":"10.15283/ijsc25141","DOIUrl":"https://doi.org/10.15283/ijsc25141","url":null,"abstract":"<p><p>The CAG expansion in the ataxin-3 (<i>ATXN3</i>) protein is the underlying cause of Spinocerebellar Ataxia Type 3 (SCA3), a polyglutamine disease. The aggregation of mutant <i>ATXN3</i> protein is hypothesized to contribute to neuronal dysfunction, neurodegeneration, or neuroinflammation. Mesenchymal stem cells have pleiotropic therapeutic properties, and adipose-derived mesenchymal stem cells (ADMSC) have been shown to be safe and well-tolerated in SCA3 patients. In this study, we evaluated the therapeutic effects of ADMSC in SCA3 mice. In a mouse model of SCA3, the Purkinje-cell-specific L7 promoter drives the expression of a truncated form of human ataxin-3 with 69 glutamine repeats. SCA3 mice exhibited cerebellar Purkinje cell degeneration, reduced myelination, and increased gliosis; pathological features also observed in SCA3 patients. SCA3 mice received repeated intravenous administrations of ADMSC, and efficacy was assessed by rotarod performance, molecular and pathological changes, and serum neurofilament light chain (NfL) levels. ADMSC-treated SCA3 mice showed significant improvements in rotarod performance, a reduction in accumulated toxic mutant <i>ATXN3</i>-69Q protein in Purkinje cells, decreased demyelination, and alleviation of neuroinflammatory and systemic inflammatory responses during disease progression. Furthermore, NfL levels, a potential biomarker for SCA3 disease progression, were inversely correlated with the rotarod performance. Based on these findings, we conclude that ADMSC enhance motor function in SCA3 mice by reducing neuroinflammation, demyelination and aggregated mutant ataxin-3 protein levels in Purkinje cells. ADMSC have the potential to serve as a disease-modifying therapy for SCA3 patients.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368364","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
Rejuvenation Potential of Developmental Genes Downregulated in Aging. 衰老过程中发育基因的返老还童潜力下调。
IF 2.4 4区 医学
International journal of stem cells Pub Date : 2026-06-10 DOI: 10.15283/ijsc25144
Byungkuk Min, Juhyeon Nam, Minseo Choi, Junyoung Hong, Areum Baek, Janghwan Kim
{"title":"Rejuvenation Potential of Developmental Genes Downregulated in Aging.","authors":"Byungkuk Min, Juhyeon Nam, Minseo Choi, Junyoung Hong, Areum Baek, Janghwan Kim","doi":"10.15283/ijsc25144","DOIUrl":"https://doi.org/10.15283/ijsc25144","url":null,"abstract":"<p><p>Partial reprogramming with Yamanaka factors effectively reverses cellular aging but poses potential oncogenic risks, limiting clinical translation. To identify safer rejuvenation induction factors (RIFs), we integrated five aging datasets and compared them with single-cell transcriptomics data from 811 mouse embryonic cells in preimplatation stages. This analysis identified genes exhibiting an inverse relationship between aging (downregulated) and development (upregulated). We further refined this selection by isolating genes common in the intermediate stage of Yamanaka factor-mediated reprogramming. Based on the molecular characteristics of reprogramming factors, we successfully isolated four RIFs associated with ribosome biogenesis, mitochondrial import, translational regulation, and serine metabolism. The expression of these RIFs in aged fibroblasts effectively reduced senescence markers and increased gene expression patterns inversely associated with aging-associated transcriptional change. Unlike the established Yamanaka factors, these identified RIFs modulate development-associated pathways that decline with aging, without activating pluripotency-associated programs, suggesting a potentially safer rejuvenation strategy.</p>","PeriodicalId":14392,"journal":{"name":"International journal of stem cells","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148211314","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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