Cell Reports Medicine最新文献_第6页

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-05-20 DOI: 10.1016/j.xcrm.2025.102142

Felicia Pagliuca

引用次数: 0

Cancer vaccine from intracellularly gelated tumor cells functionalized with CD47 blockage and damage-associated molecular pattern exposure. 细胞内凝胶化肿瘤细胞的肿瘤疫苗与CD47阻断和损伤相关的分子模式暴露。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-05-20 Epub Date: 2025-05-08 DOI: 10.1016/j.xcrm.2025.102092

Cheng Gao, Ruifeng Luo, Cheryl H T Kwong, Jinwei Liu, Mian Tang, Beibei Xie, Tianshun Duan, Ruibing Wang

{"title":"Cancer vaccine from intracellularly gelated tumor cells functionalized with CD47 blockage and damage-associated molecular pattern exposure.","authors":"Cheng Gao, Ruifeng Luo, Cheryl H T Kwong, Jinwei Liu, Mian Tang, Beibei Xie, Tianshun Duan, Ruibing Wang","doi":"10.1016/j.xcrm.2025.102092","DOIUrl":"10.1016/j.xcrm.2025.102092","url":null,"abstract":"The effectiveness of whole tumor cell vaccines prepared by traditional inactivation methodology is often hindered by insufficient immunogenicity. Here, we report development of a cancer vaccine through the intracellular gelation of tumor cells, combined with CD47 blockade and damage-associated molecular pattern (DAMP) exposure, for effective tumor prevention and treatment. Intracellular hydrogelation preserves the morphology and antigenicity of tumor cells. CD47 blockade and DAMP exposure synergistically enhance the \"eat me\" signals and inhibit the \"don't eat me\" signals on tumor cells, significantly improving their immunogenicity. In the context of tumor prevention and treatment of pre-existing tumors, this vaccine polarizes CD4+ T cells toward a TH1 phenotype, reduces regulatory T cells and T cell exhaustion, and elicits a robust tumor-antigen-specific T cell response. When combined with an immune checkpoint inhibitor, this vaccine demonstrates enhanced efficacy in eradicating established tumors. The successful application of this vaccine using ascites and subcutaneous tumor cells supports the feasibility of developing personalized whole tumor cell vaccines for diverse tumor types.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102092"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

AI-powered integration of multimodal imaging in precision medicine for neuropsychiatric disorders. 神经精神疾病精准医学中人工智能驱动的多模态成像集成。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-05-20 DOI: 10.1016/j.xcrm.2025.102132

Weijie Huang, Ni Shu

引用次数: 0

scRNA-seq reveals an immune microenvironment and JUN-mediated NK cell exhaustion in relapsed T-ALL. scRNA-seq揭示了复发性T-ALL的免疫微环境和jun介导的NK细胞衰竭。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-05-20 Epub Date: 2025-04-29 DOI: 10.1016/j.xcrm.2025.102098

Yong Liu, Zefan Du, Lindi Li, Junbin Huang, Su Liu, Bo Lu, Yifei Duan, Yucai Cheng, Tianwen Li, Jing Zhang, Jiani Mo, Yalin Yang, Wengqing Wang, Hailin Zou, Tianqi Liang, Meng Jiang, Mo Yang, Yun Chen, Cheng Ouyang, Chun Chen

{"title":"scRNA-seq reveals an immune microenvironment and JUN-mediated NK cell exhaustion in relapsed T-ALL.","authors":"Yong Liu, Zefan Du, Lindi Li, Junbin Huang, Su Liu, Bo Lu, Yifei Duan, Yucai Cheng, Tianwen Li, Jing Zhang, Jiani Mo, Yalin Yang, Wengqing Wang, Hailin Zou, Tianqi Liang, Meng Jiang, Mo Yang, Yun Chen, Cheng Ouyang, Chun Chen","doi":"10.1016/j.xcrm.2025.102098","DOIUrl":"10.1016/j.xcrm.2025.102098","url":null,"abstract":"T cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease characterized by a high relapse rate. By single-cell transcriptome analysis, we characterize the bone marrow immune microenvironment in patients with T-ALL, identifying 13 major cell clusters. These patients exhibited abnormally expanded hematopoietic stem cells (HSCs) and granulocyte-monocyte progenitors (GMPs), immunosuppressive traits in CD4+ T, CD8+ T, and natural killer (NK) cells. Subdividing CD4+ T cells reveal two subsets transitioning between T helper (Th)1/Th2, Annexin-A1 (ANXA1)-GATA3-CD4+ T, and ANXA1+GATA3+CD4+ T. Additionally, NK cells demonstrate exhaustion in the tumor microenvironment of patients with relapsed T-ALL, with JUN identified as a critical factor. Additionally, JUN is also highly expressed in T-ALL and is crucial for maintaining its proliferation. The JUN inhibitor exhibited successful lethality toward leukemia cells and ameliorated NK cell exhaustion in relapsed T-ALL cell line, as well as in cell-derived tumor xenograft (CDX), patient-derived tumor xenograft (PDX), and NOTCH1-mutant mouse models. In summary, our findings enhance the understanding of T-ALL relapse mechanisms and support the development of innovative immunotherapies for patients with relapsed T-ALL.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102098"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Tailoring an intravenously injectable oncolytic virus for augmenting radiotherapy. 为增强放射治疗量身定制静脉注射溶瘤病毒。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-05-20 Epub Date: 2025-04-14 DOI: 10.1016/j.xcrm.2025.102078

Chen Xu, Liting Chen, Guangna Liu, Jiaqi Xu, Wei Lv, Xiaoyu Gao, Peijun Xu, Ming Tang, Yaohe Wang, Xiao Zhao, Guangjun Nie, Keman Cheng, Funan Liu

{"title":"Tailoring an intravenously injectable oncolytic virus for augmenting radiotherapy.","authors":"Chen Xu, Liting Chen, Guangna Liu, Jiaqi Xu, Wei Lv, Xiaoyu Gao, Peijun Xu, Ming Tang, Yaohe Wang, Xiao Zhao, Guangjun Nie, Keman Cheng, Funan Liu","doi":"10.1016/j.xcrm.2025.102078","DOIUrl":"10.1016/j.xcrm.2025.102078","url":null,"abstract":"Oncolytic viruses (OVs) combined with radiotherapy (RT) show promise but are limited by challenges such as poor intravenous delivery and insufficient RT-induced DNA damage. In this study, an oncolytic adenovirus (AD) formulation, RadioOnco (AD@PSSP), is developed to improve delivery, infectivity, immune response, and RT efficacy. The multifunctional polyethylenimine (PEI)-selenium-polyethylene glycol (PEG) (PSSP) enhances intravenous delivery, shields the virus from rapid clearance, and enables targeted delivery to tumor sites after RT. The exposed PEI enhances the infectivity of AD through electrostatic interactions, thereby increasing DNA damage after RT by inhibiting the expression of DNA repair proteins, such as CHEK1 and CDK1. Furthermore, AD-PEI captures and delivers RT-induced tumor-released antigens to lymph nodes, activating robust anti-tumor immune responses. Animal model data demonstrate that RadioOnco overcomes RT resistance, targets distant metastases, and promotes long-term immunity, addressing metastasis and recurrence. In summary, this intravenously injectable OV enhances RT synergy through surface modification with multifunctional materials.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102078"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Targeting mitochondrial complex I of CD177⁺ neutrophils alleviates lung ischemia-reperfusion injury. 靶向CD177+中性粒细胞线粒体复合体I减轻肺缺血再灌注损伤。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-05-20 DOI: 10.1016/j.xcrm.2025.102140

Junqi Wu, Peigen Gao, Chenlu Yang, Fenghui Zhuang, Yunzhe Luo, Feng Wen, Panyu Zhang, Long Wang, Huikang Xie, Chenyang Dai, Deping Zhao, Chongwu Li, Haohao Deng, Ziqing Deng, Chang Chen

{"title":"Targeting mitochondrial complex I of CD177+ neutrophils alleviates lung ischemia-reperfusion injury.","authors":"Junqi Wu, Peigen Gao, Chenlu Yang, Fenghui Zhuang, Yunzhe Luo, Feng Wen, Panyu Zhang, Long Wang, Huikang Xie, Chenyang Dai, Deping Zhao, Chongwu Li, Haohao Deng, Ziqing Deng, Chang Chen","doi":"10.1016/j.xcrm.2025.102140","DOIUrl":"10.1016/j.xcrm.2025.102140","url":null,"abstract":"Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality following lung transplantation, with neutrophils playing a central role in its inflammatory pathology. Here, we employ single-cell RNA sequencing and spatial transcriptomics to investigate neutrophil subtypes in the lung ischemia-reperfusion injury (IRI) model. We identify CD177+ neutrophils as an activated subpopulation that significantly contributes to lung injury and serves as an early biomarker for predicting severe PGD in human lung transplant recipients (area under the curve [AUC] = 0.871). CD177+ neutrophils exhibit elevated oxidative phosphorylation and increased mitochondrial complex I activity, driving inflammation and the formation of neutrophil extracellular traps. Targeting mitochondrial function with the complex I inhibitor IACS-010759 reduces CD177+ neutrophil activation and alleviates lung injury in both mouse IRI and rat left lung transplant models. These findings provide a comprehensive landscape of CD177+ neutrophil-driven inflammation in lung IRI and highlight its potential value for future early diagnosis and therapeutic interventions.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":"6 5","pages":"102140"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Efficacy of a postbiotic and its components in promoting colonic transit and alleviating chronic constipation in humans and mice. 一种后生物制剂及其成分在促进人类和小鼠结肠运输和缓解慢性便秘中的功效。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-05-20 Epub Date: 2025-04-25 DOI: 10.1016/j.xcrm.2025.102093

Teng Ma, Yalin Li, Ni Yang, Huan Wang, Xuan Shi, Yanfang Liu, Hao Jin, Lai-Yu Kwok, Zhihong Sun, Heping Zhang

{"title":"Efficacy of a postbiotic and its components in promoting colonic transit and alleviating chronic constipation in humans and mice.","authors":"Teng Ma, Yalin Li, Ni Yang, Huan Wang, Xuan Shi, Yanfang Liu, Hao Jin, Lai-Yu Kwok, Zhihong Sun, Heping Zhang","doi":"10.1016/j.xcrm.2025.102093","DOIUrl":"10.1016/j.xcrm.2025.102093","url":null,"abstract":"This study evaluates the efficacy of the postbiotic Probio-Eco in alleviating constipation in humans and mice. A randomized, double-blind, placebo-controlled crossover trial involving 110 adults with chronic constipation (Rome IV criteria) demonstrates that a 3-week Probio-Eco intervention significantly improves constipation symptoms, stool straining, and worry scores. Gut microbiota and metabolomic analyses reveal modulations in specific gut microbiota, succinate, tryptophan derivatives, deoxycholate, propionate, butyrate, and cortisol, correlating with symptom relief. A loperamide-induced mouse model confirms that Probio-Eco and its bioactive components (succinate, 3-indoleacrylic acid, and 5-hydroxytryptophan) alleviate constipation by stimulating mucin-2 secretion, regulating intestinal transport hormones, and promoting anti-inflammatory responses. Multi-omics integration identifies key pathways, including succinate-short-chain fatty acid, tryptophan-5-hydroxytryptophan-serotonin, and tryptophan-3-indoleacrylic acid, driving intestinal homeostasis and motility. These findings highlight the comprehensive efficacy of Probio-Eco and provide robust evidence for its clinical application in constipation management. This study was registered at Chinese Clinical Trial Registry (ChiCTR2100054376).","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102093"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 structural haplotype in the 17q21.31 MAPT region is associated with increased risk for chronic traumatic encephalopathy endophenotypes. 17q21.31 MAPT区域的结构单倍型与慢性创伤性脑病内表型的风险增加有关。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-05-20 Epub Date: 2025-04-15 DOI: 10.1016/j.xcrm.2025.102084

Xudong Han, Yichi Zhang, Jillian N Petrosky, Sarah Bald, Richard M Sherva, Adam Labadorf, Jonathan D Cherry, Jaeyoon Chung, Kurt Farrell, Bobak Abdolmohammadi, Shruti Durape, Brett M Martin, Joseph N Palmisano, John J Farrell, Victor E Alvarez, Bertrand R Huber, Brigid Dwyer, Daniel H Daneshvar, Kristen Dams-O'Connor, Gyungah R Jun, Kathryn L Lunetta, Lee E Goldstein, Douglas I Katz, Robert C Cantu, Martha E Shenton, Jeffrey L Cummings, Eric M Reiman, Robert A Stern, Michael L Alosco, Yorghos Tripodis, Lindsay A Farrer, Thor D Stein, John F Crary, Ann C McKee, Jesse Mez

{"title":"A structural haplotype in the 17q21.31 MAPT region is associated with increased risk for chronic traumatic encephalopathy endophenotypes.","authors":"Xudong Han, Yichi Zhang, Jillian N Petrosky, Sarah Bald, Richard M Sherva, Adam Labadorf, Jonathan D Cherry, Jaeyoon Chung, Kurt Farrell, Bobak Abdolmohammadi, Shruti Durape, Brett M Martin, Joseph N Palmisano, John J Farrell, Victor E Alvarez, Bertrand R Huber, Brigid Dwyer, Daniel H Daneshvar, Kristen Dams-O'Connor, Gyungah R Jun, Kathryn L Lunetta, Lee E Goldstein, Douglas I Katz, Robert C Cantu, Martha E Shenton, Jeffrey L Cummings, Eric M Reiman, Robert A Stern, Michael L Alosco, Yorghos Tripodis, Lindsay A Farrer, Thor D Stein, John F Crary, Ann C McKee, Jesse Mez","doi":"10.1016/j.xcrm.2025.102084","DOIUrl":"10.1016/j.xcrm.2025.102084","url":null,"abstract":"Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. Genetic variation in the 17q21.31 region, containing microtubule-associated protein tau (MAPT), has been implicated in tauopathies but has not been investigated in CTE. The region includes a megabase-long inversion (H1/H2) and copy-number variations, including α, β, and γ segments, which can be characterized as nine segregating structural haplotypes. We leveraged array SNP data and a reference panel across the 17q21.31 region to impute structural haplotypes and test their association with CTE endophenotypes in 447 European ancestry brain donors with RHI exposure. The H1β1γ1 haplotype was significantly associated with dementia and semi-quantitative tau burden in multiple cortical and medial temporal regions commonly affected in CTE. H1β1γ1 differential expression analyses in dorsolateral frontal cortex implicated cis-acting genes and inflammatory pathways. Taken together, the H1β1γ1 haplotype may help explain CTE heterogeneity among those with similar RHI exposure.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102084"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Integrated liver-secreted and plasma proteomics identify a predictive model that stratifies MASH. 综合肝分泌和血浆蛋白质组学确定了分层MASH的预测模型。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-05-20 Epub Date: 2025-04-17 DOI: 10.1016/j.xcrm.2025.102085

William De Nardo, Olivia Lee, Yazmin Johari, Jacqueline Bayliss, Marcus Pensa, Paula M Miotto, Stacey N Keenan, Andrew Ryan, Amber Rucinski, Tessa M Svinos, Geraldine J Ooi, Wendy A Brown, William Kemp, Stuart K Roberts, Benjamin L Parker, Magdalene K Montgomery, Mark Larance, Paul R Burton, Matthew J Watt

{"title":"Integrated liver-secreted and plasma proteomics identify a predictive model that stratifies MASH.","authors":"William De Nardo, Olivia Lee, Yazmin Johari, Jacqueline Bayliss, Marcus Pensa, Paula M Miotto, Stacey N Keenan, Andrew Ryan, Amber Rucinski, Tessa M Svinos, Geraldine J Ooi, Wendy A Brown, William Kemp, Stuart K Roberts, Benjamin L Parker, Magdalene K Montgomery, Mark Larance, Paul R Burton, Matthew J Watt","doi":"10.1016/j.xcrm.2025.102085","DOIUrl":"10.1016/j.xcrm.2025.102085","url":null,"abstract":"Obesity is a major risk factor for metabolic-associated steatotic liver disease (MASLD), which can progress to metabolic-associated steatohepatitis (MASH). There are no validated non-invasive tests to stratify persons with obesity with a greater risk for MASH. Herein, we assess plasma and liver from 266 obese individuals spanning the MASLD spectrum. Ninety-six human livers were precision-cut, and mass spectrometry-based proteomics identifies 3,333 proteins in the liver-secretion medium, of which 107 are differentially secreted in MASH compared with no pathology. The plasma proteome is markedly remodeled in MASH but is not different between patients with steatosis and no pathology. The APASHA model, comprising plasma apolipoprotein F (APOF), proprotein convertase subtilisin/kexin type 9 (PCSK9), afamin (AFM), S100 calcium-binding protein A6 (S100A6), HbA1c, and zinc-alpha-2-glycoprotein (AZGP1), stratifies MASH (area under receiver operating characteristic [AUROC] = 0.88). Our investigations detail the evolution of liver-secreted and plasma proteins with MASLD progression, providing a rich resource defining human liver-secreted proteins and creating a predictive model to stratify patients with obesity at risk of MASH.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102085"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

RSPO1, a potent inducer of pancreatic β cell neogenesis. RSPO1，胰腺β细胞新生的有效诱导剂。

IF 11.7 1区医学

Cell Reports Medicine Pub Date : 2025-05-20 Epub Date: 2025-05-07 DOI: 10.1016/j.xcrm.2025.102126

Serena Silvano, Tiziana Napolitano, Magali Plaisant, Anette Sousa-De-Veiga, Hugo Fofo, Chaïma Ayachi, Benoit Allegrini, Samah Rekima, Estelle Pichery, Jérôme Becam, Valentin Lepage, Caroline Treins, Laura Etasse, Loan Tran, Julien Thévenet, Gianni Pasquetti, Julie Kerr-Conte, François Pattou, Paolo Botti, Arduino Arduini, Jacques Mizrahi, Benjamin Charles, Patrick Collombat

{"title":"RSPO1, a potent inducer of pancreatic β cell neogenesis.","authors":"Serena Silvano, Tiziana Napolitano, Magali Plaisant, Anette Sousa-De-Veiga, Hugo Fofo, Chaïma Ayachi, Benoit Allegrini, Samah Rekima, Estelle Pichery, Jérôme Becam, Valentin Lepage, Caroline Treins, Laura Etasse, Loan Tran, Julien Thévenet, Gianni Pasquetti, Julie Kerr-Conte, François Pattou, Paolo Botti, Arduino Arduini, Jacques Mizrahi, Benjamin Charles, Patrick Collombat","doi":"10.1016/j.xcrm.2025.102126","DOIUrl":"10.1016/j.xcrm.2025.102126","url":null,"abstract":"Inducing the neogenesis of pancreatic insulin-producing β cells holds great promise for diabetes research. However, non-toxic compounds with such activities remain to be discovered. Herein, we report the identification of RSPO1, a key agonist of the Wnt/β-catenin pathway, as an inducer of β cell replication. Specifically, we provide evidence that RSPO1 promotes a significant increase in β cell neogenesis in vitro, ex vivo, and in vivo. Importantly, RSPO1 administration is sufficient to activate Wnt/β-catenin signaling in β cells and counter chemically induced or autoimmune-mediated diabetes. Similarly, an optimized analog of RSPO1, allowing for weekly administration, also prevents diabetes in vivo. Lastly, the treatment of transplanted human islets with RSPO1 induces a significant 2.78-fold increase in human β cell numbers in only 60 days, these cells being functional. Such activities of RSPO1 to promote β cell neogenesis could therefore represent an unprecedented hope in the continued search for diabetes alternative therapies.","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102126"},"PeriodicalIF":11.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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