Cell stem cell最新文献_第2页

Preclinical efficacy and safety of encapsulated proliferating human hepatocyte organoids in treating liver failure. 封装增殖人肝细胞器官组织治疗肝衰竭的临床前疗效和安全性。

Cell stem cell Pub Date : 2024-04-04 Epub Date: 2024-03-07 DOI: 10.1016/j.stem.2024.02.005

Xiang Yuan, Jingqi Wu, Zhen Sun, Jin Cen, Yajing Shu, Chenhua Wang, Hong Li, Dongni Lin, Kun Zhang, Baihua Wu, Anil Dhawan, Ludi Zhang, Lijian Hui

{"title":"Preclinical efficacy and safety of encapsulated proliferating human hepatocyte organoids in treating liver failure.","authors":"Xiang Yuan, Jingqi Wu, Zhen Sun, Jin Cen, Yajing Shu, Chenhua Wang, Hong Li, Dongni Lin, Kun Zhang, Baihua Wu, Anil Dhawan, Ludi Zhang, Lijian Hui","doi":"10.1016/j.stem.2024.02.005","DOIUrl":"10.1016/j.stem.2024.02.005","url":null,"abstract":"Alginate-encapsulated hepatocyte transplantation is a promising strategy to treat liver failure. However, its clinical application was impeded by the lack of primary human hepatocytes and difficulty in controlling their quality. We previously reported proliferating human hepatocytes (ProliHHs). Here, quality-controlled ProliHHs were produced in mass and engineered as liver organoids to improve their maturity. Encapsulated ProliHHs liver organoids (eLO) were intraperitoneally transplanted to treat liver failure animals. Notably, eLO treatment increased the survival of mice with post-hepatectomy liver failure (PHLF) and ameliorated hyperammonemia and hypoglycemia by providing liver functions. Additionally, eLO treatment protected the gut from PHLF-augmented permeability and normalized the increased serum endotoxin and inflammatory response, which facilitated liver regeneration. The therapeutic effect of eLO was additionally proved in acetaminophen-induced liver failure. Furthermore, we performed assessments of toxicity and biodistribution, demonstrating that eLO had no adverse effects on animals and remained non-tumorigenic.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"484-498.e5"},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140066369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Autofluorescence is a biomarker of neural stem cell activation state. 自发荧光是神经干细胞活化状态的生物标记。

Cell stem cell Pub Date : 2024-04-04 Epub Date: 2024-03-22 DOI: 10.1016/j.stem.2024.02.011

Christopher S Morrow, Kelsey Tweed, Sabina Farhadova, Alex J Walsh, Bo P Lear, Avtar Roopra, Ryan D Risgaard, Payton C Klosa, Zachary P Arndt, Ella R Peterson, Michelle M Chi, Allison G Harris, Melissa C Skala, Darcie L Moore

{"title":"Autofluorescence is a biomarker of neural stem cell activation state.","authors":"Christopher S Morrow, Kelsey Tweed, Sabina Farhadova, Alex J Walsh, Bo P Lear, Avtar Roopra, Ryan D Risgaard, Payton C Klosa, Zachary P Arndt, Ella R Peterson, Michelle M Chi, Allison G Harris, Melissa C Skala, Darcie L Moore","doi":"10.1016/j.stem.2024.02.011","DOIUrl":"10.1016/j.stem.2024.02.011","url":null,"abstract":"Neural stem cells (NSCs) must exit quiescence to produce neurons; however, our understanding of this process remains constrained by the technical limitations of current technologies. Fluorescence lifetime imaging (FLIM) of autofluorescent metabolic cofactors has been used in other cell types to study shifts in cell states driven by metabolic remodeling that change the optical properties of these endogenous fluorophores. Using this non-destructive, live-cell, and label-free strategy, we found that quiescent NSCs (qNSCs) and activated NSCs (aNSCs) have unique autofluorescence profiles. Specifically, qNSCs display an enrichment of autofluorescence localizing to a subset of lysosomes, which can be used as a graded marker of NSC quiescence to predict cell behavior at single-cell resolution. Coupling autofluorescence imaging with single-cell RNA sequencing, we provide resources revealing transcriptional features linked to deep quiescence and rapid NSC activation. Together, we describe an approach for tracking mouse NSC activation state and expand our understanding of adult neurogenesis.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"570-581.e7"},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140195314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of CRISPR/HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques. CRISPR/HDR 编辑与慢病毒转导对猕猴 HSPCs 长期移植和克隆动态的影响。

Cell stem cell Pub Date : 2024-04-04 Epub Date: 2024-03-19 DOI: 10.1016/j.stem.2024.02.010

Byung-Chul Lee, Ashley Gin, Chuanfeng Wu, Komudi Singh, Max Grice, Ryland Mortlock, Diana Abraham, Xing Fan, Yifan Zhou, Aisha AlJanahi, Uimook Choi, Suk See DeRavin, Taehoon Shin, Sogun Hong, Cynthia E Dunbar

{"title":"Impact of CRISPR/HDR editing versus lentiviral transduction on long-term engraftment and clonal dynamics of HSPCs in rhesus macaques.","authors":"Byung-Chul Lee, Ashley Gin, Chuanfeng Wu, Komudi Singh, Max Grice, Ryland Mortlock, Diana Abraham, Xing Fan, Yifan Zhou, Aisha AlJanahi, Uimook Choi, Suk See DeRavin, Taehoon Shin, Sogun Hong, Cynthia E Dunbar","doi":"10.1016/j.stem.2024.02.010","DOIUrl":"10.1016/j.stem.2024.02.010","url":null,"abstract":"For precise genome editing via CRISPR/homology-directed repair (HDR), effective and safe editing of long-term engrafting hematopoietic stem cells (LT-HSCs) is required. The impact of HDR on true LT-HSC clonal dynamics in a relevant large animal model has not been studied. To track the output and clonality of HDR-edited cells and to provide a comparison to lentivirally transduced HSCs in vivo, we developed a competitive rhesus macaque (RM) autologous transplantation model, co-infusing HSCs transduced with a barcoded GFP-expressing lentiviral vector (LV) and HDR edited at the CD33 locus. CRISPR/HDR-edited cells showed a two-log decrease by 2 months following transplantation, with little improvement via p53 inhibition, in comparison to minimal loss of LV-transduced cells long term. HDR long-term clonality was oligoclonal in contrast to highly polyclonal LV-transduced HSCs. These results suggest marked clinically relevant differences in the impact of current genetic modification approaches on HSCs.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":" ","pages":"455-466.e4"},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10997443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140178235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Strengthening cardiac therapy pipelines using human pluripotent stem cell-derived cardiomyocytes. 利用人体多能干细胞衍生的心肌细胞加强心脏治疗管道。

Cell stem cell Pub Date : 2024-03-07 Epub Date: 2024-02-15 DOI: 10.1016/j.stem.2024.01.007

Kavita Raniga, Aishah Nasir, Nguyen T N Vo, Ravi Vaidyanathan, Sarah Dickerson, Simon Hilcove, Diogo Mosqueira, Gary R Mirams, Peter Clements, Ryan Hicks, Amy Pointon, Will Stebbeds, Jo Francis, Chris Denning

引用次数: 0

Hypoimmune islets achieve insulin independence after allogeneic transplantation in a fully immunocompetent non-human primate. 免疫力低下的胰岛在完全免疫功能健全的非人灵长类动物体内进行异体移植后实现了胰岛素独立性。

Cell stem cell Pub Date : 2024-03-07 Epub Date: 2024-02-08 DOI: 10.1016/j.stem.2024.02.001

Xiaomeng Hu, Kathy White, Chi Young, Ari G Olroyd, Paul Kievit, Andrew J Connolly, Tobias Deuse, Sonja Schrepfer

引用次数: 0

Large structural variants in KOLF2.1J are unlikely to compromise neurological disease modeling. KOLF2.1J的大结构变异不太可能影响神经系统疾病的建模。

Cell stem cell Pub Date : 2024-03-07 DOI: 10.1016/j.stem.2024.02.006

Mallory Ryan, Justin A McDonough, Michael E Ward, Mark R Cookson, William C Skarnes, Florian T Merkle

引用次数: 0

A mitochondrial NADPH-cholesterol axis regulates extracellular vesicle biogenesis to support hematopoietic stem cell fate. 线粒体 NADPH-胆固醇轴调节细胞外囊泡的生物生成，支持造血干细胞的命运。

Cell stem cell Pub Date : 2024-03-07 DOI: 10.1016/j.stem.2024.02.004

Massimo Bonora, Claudia Morganti, Nick van Gastel, Kyoko Ito, Enrica Calura, Ilaria Zanolla, Letizia Ferroni, Yang Zhang, Yookyung Jung, Gabriele Sales, Paolo Martini, Takahisa Nakamura, Francesco Massimo Lasorsa, Toren Finkel, Charles P Lin, Barbara Zavan, Paolo Pinton, Irene Georgakoudi, Chiara Romualdi, David T Scadden, Keisuke Ito

{"title":"A mitochondrial NADPH-cholesterol axis regulates extracellular vesicle biogenesis to support hematopoietic stem cell fate.","authors":"Massimo Bonora, Claudia Morganti, Nick van Gastel, Kyoko Ito, Enrica Calura, Ilaria Zanolla, Letizia Ferroni, Yang Zhang, Yookyung Jung, Gabriele Sales, Paolo Martini, Takahisa Nakamura, Francesco Massimo Lasorsa, Toren Finkel, Charles P Lin, Barbara Zavan, Paolo Pinton, Irene Georgakoudi, Chiara Romualdi, David T Scadden, Keisuke Ito","doi":"10.1016/j.stem.2024.02.004","DOIUrl":"10.1016/j.stem.2024.02.004","url":null,"abstract":"Mitochondrial fatty acid oxidation (FAO) is essential for hematopoietic stem cell (HSC) self-renewal; however, the mechanism by which mitochondrial metabolism controls HSC fate remains unknown. Here, we show that within the hematopoietic lineage, HSCs have the largest mitochondrial NADPH pools, which are required for proper HSC cell fate and homeostasis. Bioinformatic analysis of the HSC transcriptome, biochemical assays, and genetic inactivation of FAO all indicate that FAO-generated NADPH fuels cholesterol synthesis in HSCs. Interference with FAO disturbs the segregation of mitochondrial NADPH toward corresponding daughter cells upon single HSC division. Importantly, we have found that the FAO-NADPH-cholesterol axis drives extracellular vesicle (EV) biogenesis and release in HSCs, while inhibition of EV signaling impairs HSC self-renewal. These data reveal the existence of a mitochondrial NADPH-cholesterol axis for EV biogenesis that is required for hematopoietic homeostasis and highlight the non-stochastic nature of HSC fate determination.","PeriodicalId":93928,"journal":{"name":"Cell stem cell","volume":"31 3","pages":"359-377.e10"},"PeriodicalIF":0.0,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10957094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140066370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From suppressor to enhancer: IL-10's alternative role in CAR-T cell therapies against solid tumors. 从抑制剂到增强剂：IL-10 在 CAR-T 细胞疗法中对实体瘤的替代作用。

Cell stem cell Pub Date : 2024-03-07 DOI: 10.1016/j.stem.2024.02.003

Yuwei Huang, Haopeng Wang

引用次数: 0

Development has the answer: Unraveling psychiatric disorders via thalamocortical organoids. 发育有了答案：通过丘脑皮层有机体揭开精神疾病的神秘面纱

Cell stem cell Pub Date : 2024-03-07 DOI: 10.1016/j.stem.2024.02.008

Eduardo Leyva-Díaz, Emily S Wilson, Guillermina López-Bendito

引用次数: 0

Promises and challenges of organoids: From humanized to human derived. 有机体的前景与挑战：从 "人源化 "到 "人源化"。

Cell stem cell Pub Date : 2024-03-07 DOI: 10.1016/j.stem.2024.02.002

Wenyan Wang, Yang-Xin Fu

引用次数: 0