Cell stem cell最新文献_第10页

Pluripotent stem-cell-derived therapies in clinical trial: A 2025 update 临床试验中的多能干细胞衍生疗法：2025年更新

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-01-02 DOI: 10.1016/j.stem.2024.12.005

Agnete Kirkeby, Heather Main, Melissa Carpenter

引用次数: 0

All-in-one gene therapy alternative for DBAS DBAS的一体化基因治疗方案

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-01-02 DOI: 10.1016/j.stem.2024.12.003

Susana Navarro, Paula Río

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Engineered hiPSC-derived vascular graft brings hope for thrombosis-free vascular therapy 工程hipsc衍生血管移植物为无血栓形成的血管治疗带来希望

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-01-02 DOI: 10.1016/j.stem.2024.12.001

Soniya Tamhankar, Eric V. Shusta, Sean P. Palecek

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Perceiving the brain like never before 以前所未有的方式感知大脑

IF 23.9 1区医学

Cell stem cell Pub Date : 2025-01-02 DOI: 10.1016/j.stem.2024.12.004

Sarah Stanley

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Spatiotemporal single-cell roadmap of human skin wound healing 人体皮肤伤口愈合的时空单细胞路线图

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-12-26 DOI: 10.1016/j.stem.2024.11.013

Zhuang Liu, Xiaowei Bian, Lihua Luo, Åsa K. Björklund, Li Li, Letian Zhang, Yongjian Chen, Lei Guo, Juan Gao, Chunyan Cao, Jiating Wang, Wenjun He, Yunting Xiao, Liping Zhu, Karl Annusver, Nusayhah Hudaa Gopee, Daniela Basurto-Lozada, David Horsfall, Clare L. Bennett, Maria Kasper, Ning Xu Landén

{"title":"Spatiotemporal single-cell roadmap of human skin wound healing","authors":"Zhuang Liu, Xiaowei Bian, Lihua Luo, Åsa K. Björklund, Li Li, Letian Zhang, Yongjian Chen, Lei Guo, Juan Gao, Chunyan Cao, Jiating Wang, Wenjun He, Yunting Xiao, Liping Zhu, Karl Annusver, Nusayhah Hudaa Gopee, Daniela Basurto-Lozada, David Horsfall, Clare L. Bennett, Maria Kasper, Ning Xu Landén","doi":"10.1016/j.stem.2024.11.013","DOIUrl":"https://doi.org/10.1016/j.stem.2024.11.013","url":null,"abstract":"Wound healing is vital for human health, yet the details of cellular dynamics and coordination in human wound repair remain largely unexplored. To address this, we conducted single-cell multi-omics analyses on human skin wound tissues through inflammation, proliferation, and remodeling phases of wound repair from the same individuals, monitoring the cellular and molecular dynamics of human skin wound healing at an unprecedented spatiotemporal resolution. This singular roadmap reveals the cellular architecture of the wound margin and identifies FOSL1 as a critical driver of re-epithelialization. It shows that pro-inflammatory macrophages and fibroblasts sequentially support keratinocyte migration like a relay race across different healing stages. Comparison with single-cell data from venous and diabetic foot ulcers uncovers a link between failed keratinocyte migration and impaired inflammatory response in chronic wounds. Additionally, comparing human and mouse acute wound transcriptomes underscores the indispensable value of this roadmap in bridging basic research with clinical innovations.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"18 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Different effects of fatty acid oxidation on hematopoietic stem cells based on age and diet 脂肪酸氧化对造血干细胞的不同影响基于年龄和饮食

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-12-20 DOI: 10.1016/j.stem.2024.11.014

Salma Merchant, Animesh Paul, Amanda Reyes, Daniel Cassidy, Ashley Leach, Dohun Kim, Sarah Muh, Gerik Grabowski, Gerta Hoxhaj, Zhiyu Zhao, Sean J. Morrison

{"title":"Different effects of fatty acid oxidation on hematopoietic stem cells based on age and diet","authors":"Salma Merchant, Animesh Paul, Amanda Reyes, Daniel Cassidy, Ashley Leach, Dohun Kim, Sarah Muh, Gerik Grabowski, Gerta Hoxhaj, Zhiyu Zhao, Sean J. Morrison","doi":"10.1016/j.stem.2024.11.014","DOIUrl":"https://doi.org/10.1016/j.stem.2024.11.014","url":null,"abstract":"Fatty acid oxidation is of uncertain importance in most stem cells. We show by 14C-palmitate tracing and metabolomic analysis that hematopoietic stem/progenitor cells (HSPCs) engage in long-chain fatty acid oxidation that depends upon carnitine palmitoyltransferase 1a (CPT1a) and hydroxyacyl-CoA dehydrogenase (HADHA) enzymes. CPT1a or HADHA deficiency had little or no effect on HSPCs or hematopoiesis in young adult mice. Young HSPCs had the plasticity to oxidize other substrates, including glutamine, and compensated for loss of fatty acid oxidation by decreasing pyruvate dehydrogenase phosphorylation, which should increase function. This metabolic plasticity declined as mice aged, when CPT1a or HADHA deficiency altered hematopoiesis and impaired hematopoietic stem cell (HSC) function upon serial transplantation. A high-fat diet increased fatty acid oxidation and reduced HSC function. This was rescued by CPT1a or HADHA deficiency, demonstrating that increased fatty acid oxidation can undermine HSC function. Long-chain fatty acid oxidation is thus dispensable in young HSCs but necessary during aging and deleterious with a high-fat diet.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"23 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells 没有体外培养的基因编辑避免了人类造血干细胞的遗传毒性

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-12-12 DOI: 10.1016/j.stem.2024.11.001

Jing Zeng, My Anh Nguyen, Pengpeng Liu, Lucas Ferreira da Silva, Sébastien Levesque, Linda Y. Lin, David G. Justus, Karl Petri, Kendell Clement, Shaina N. Porter, Archana Verma, Nola R. Neri, Tolulope Rosanwo, Marioara-Felicia Ciuculescu, Daniela Abriss, Esther Mintzer, Stacy A. Maitland, Selami Demirci, Hye Ji Cha, Stuart H. Orkin, Daniel E. Bauer

{"title":"Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells","authors":"Jing Zeng, My Anh Nguyen, Pengpeng Liu, Lucas Ferreira da Silva, Sébastien Levesque, Linda Y. Lin, David G. Justus, Karl Petri, Kendell Clement, Shaina N. Porter, Archana Verma, Nola R. Neri, Tolulope Rosanwo, Marioara-Felicia Ciuculescu, Daniela Abriss, Esther Mintzer, Stacy A. Maitland, Selami Demirci, Hye Ji Cha, Stuart H. Orkin, Daniel E. Bauer","doi":"10.1016/j.stem.2024.11.001","DOIUrl":"https://doi.org/10.1016/j.stem.2024.11.001","url":null,"abstract":"Gene editing the BCL11A erythroid enhancer is a validated approach to fetal hemoglobin (HbF) induction for β-hemoglobinopathy therapy, though heterogeneity in edit allele distribution and HbF response may impact its safety and efficacy. Here, we compare combined CRISPR-Cas9 editing of the BCL11A +58 and +55 enhancers with leading gene modification approaches under clinical investigation. Dual targeting of the BCL11A +58 and +55 enhancers with 3xNLS-SpCas9 and two single guide RNAs (sgRNAs) resulted in superior HbF induction, including in sickle cell disease (SCD) patient xenografts, attributable to simultaneous disruption of core half E-box/GATA motifs at both enhancers. Unintended on-target outcomes of double-strand break (DSB) repair in hematopoietic stem and progenitor cells (HSPCs), such as long deletions and centromere-distal chromosome fragment loss, are a byproduct of cellular proliferation stimulated by ex vivo culture. Editing quiescent HSPCs bypasses long deletion and micronuclei formation and preserves efficient on-target editing and engraftment function.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"21 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Maternal gut microbiota influence stem cell function in offspring 母体肠道微生物群影响后代干细胞功能

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-12-11 DOI: 10.1016/j.stem.2024.10.003

Haiyue Dang, Panpan Feng, Shuning Zhang, Lihua Peng, Shuli Xing, Yuchen Li, Xiang Wen, Liqiang Zhou, Shyamal Goswami, Mingbing Xiao, Nick Barker, Philippe Sansonetti, Parag Kundu

{"title":"Maternal gut microbiota influence stem cell function in offspring","authors":"Haiyue Dang, Panpan Feng, Shuning Zhang, Lihua Peng, Shuli Xing, Yuchen Li, Xiang Wen, Liqiang Zhou, Shyamal Goswami, Mingbing Xiao, Nick Barker, Philippe Sansonetti, Parag Kundu","doi":"10.1016/j.stem.2024.10.003","DOIUrl":"https://doi.org/10.1016/j.stem.2024.10.003","url":null,"abstract":"The maternal microbiome influences child health. However, its impact on a given offspring’s stem cells, which regulate development, remains poorly understood. To investigate the role of the maternal microbiome in conditioning the offspring’s stem cells, we manipulated maternal microbiota using Akkermansia muciniphila. Different maternal microbiomes had distinct effects on proliferation and differentiation of neuronal and intestinal stem cells in the offspring, influencing their developmental trajectory, physiology, and long-term health. Transplantation of altered maternal microbiota into germ-free mice transmitted these stem cell phenotypes to the recipients’ offspring. The progeny of germ-free mice selectively colonized with Akkermansia did not display these stem cell traits, emphasizing the importance of microbiome diversity. Metabolically more active maternal microbiomes enriched the levels of circulating short-chain fatty acids (SCFAs) and amino acids, leaving distinct transcriptomic imprints on the mTOR pathway of offsprings’ stem cells. Blocking mTOR signaling during pregnancy eliminated the maternal-microbiome-mediated effects on stem cells. These results suggest a fundamental role of the maternal microbiome in programming offsprings’ stem cells and represent a promising target for interventions.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"5 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Generation of self-organized neuromusculoskeletal tri-tissue organoids from human pluripotent stem cells 从人多能干细胞生成自组织神经肌肉骨骼三组织类器官

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-12-09 DOI: 10.1016/j.stem.2024.11.005

Yao Yin, Wei Zhou, Jinkui Zhu, Ziling Chen, Linlin Jiang, Xuran Zhuang, Jia Chen, Jianfeng Wei, Xiaoxiang Lu, Yantong Liu, Wei Pang, Qinzhi Zhang, Yajing Cao, Zhuoya Li, Yuyan Zhu, Yangfei Xiang

{"title":"Generation of self-organized neuromusculoskeletal tri-tissue organoids from human pluripotent stem cells","authors":"Yao Yin, Wei Zhou, Jinkui Zhu, Ziling Chen, Linlin Jiang, Xuran Zhuang, Jia Chen, Jianfeng Wei, Xiaoxiang Lu, Yantong Liu, Wei Pang, Qinzhi Zhang, Yajing Cao, Zhuoya Li, Yuyan Zhu, Yangfei Xiang","doi":"10.1016/j.stem.2024.11.005","DOIUrl":"https://doi.org/10.1016/j.stem.2024.11.005","url":null,"abstract":"The human body function requires crosstalk between different tissues. An essential crosstalk is in the neuromusculoskeletal (NMS) axis involving neural, muscular, and skeletal tissues, which is challenging to model using human cells. Here, we describe the generation of three-dimensional, NMS tri-tissue organoids (hNMSOs) from human pluripotent stem cells through a co-development strategy. Staining, single-nucleus RNA sequencing, and spatial transcriptome profiling revealed the co-emergence and self-organization of neural, muscular, and skeletal lineages within individual organoids, and the neural domains of hNMSOs obtained a ventral-specific identity and produced motor neurons innervating skeletal muscles. The neural, muscular, and skeletal regions of hNMSOs exhibited maturation and established functional connections during development. Notably, structural, functional, and transcriptomic analyses revealed that skeletal support in hNMSOs benefited human muscular development. Modeling with hNMSOs also unveiled the neuromuscular alterations following pathological skeletal degeneration. Together, our study provides an accessible experimental model for future studies of human NMS crosstalk and abnormality.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"14 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Patient-derived glioblastoma organoids as real-time avatars for assessing responses to clinical CAR-T cell therapy 患者来源的胶质母细胞瘤类器官作为评估临床CAR-T细胞治疗反应的实时化身

IF 23.9 1区医学

Cell stem cell Pub Date : 2024-12-09 DOI: 10.1016/j.stem.2024.11.010

Meghan Logun, Xin Wang, Yusha Sun, Stephen J. Bagley, Nannan Li, Arati Desai, Daniel Y. Zhang, MacLean P. Nasrallah, Emily Ling-Lin Pai, Bike Su Oner, Gabriela Plesa, Donald Siegel, Zev A. Binder, Guo-li Ming, Hongjun Song, Donald M. O’Rourke

{"title":"Patient-derived glioblastoma organoids as real-time avatars for assessing responses to clinical CAR-T cell therapy","authors":"Meghan Logun, Xin Wang, Yusha Sun, Stephen J. Bagley, Nannan Li, Arati Desai, Daniel Y. Zhang, MacLean P. Nasrallah, Emily Ling-Lin Pai, Bike Su Oner, Gabriela Plesa, Donald Siegel, Zev A. Binder, Guo-li Ming, Hongjun Song, Donald M. O’Rourke","doi":"10.1016/j.stem.2024.11.010","DOIUrl":"https://doi.org/10.1016/j.stem.2024.11.010","url":null,"abstract":"Patient-derived tumor organoids have been leveraged for disease modeling and preclinical studies but rarely applied in real time to aid with interpretation of patient treatment responses in clinics. We recently demonstrated early efficacy signals in a first-in-human, phase 1 study of dual-targeting chimeric antigen receptor (CAR)-T cells (EGFR-IL13Rα2 CAR-T cells) in patients with recurrent glioblastoma. Here, we analyzed six sets of patient-derived glioblastoma organoids (GBOs) treated concurrently with the same autologous CAR-T cell products as patients in our phase 1 study. We found that CAR-T cell treatment led to target antigen reduction and cytolysis of tumor cells in GBOs, the degree of which correlated with CAR-T cell engraftment detected in patients’ cerebrospinal fluid (CSF). Furthermore, cytokine release patterns in GBOs mirrored those in patient CSF samples over time. Our findings highlight a unique trial design and GBOs as a valuable platform for real-time assessment of CAR-T cell bioactivity and insights into immunotherapy efficacy.","PeriodicalId":9665,"journal":{"name":"Cell stem cell","volume":"90 1","pages":""},"PeriodicalIF":23.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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