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A patient-derived T cell lymphoma biorepository uncovers pathogenetic mechanisms and host-related therapeutic vulnerabilities. 患者源性T细胞淋巴瘤生物库揭示了发病机制和宿主相关的治疗脆弱性。
IF 11.7 1区 医学
Cell Reports Medicine Pub Date : 2025-03-24 DOI: 10.1016/j.xcrm.2025.102029
Danilo Fiore, Luca Vincenzo Cappelli, Liu Zhaoqi, Nikita Kotlov, Maria Sorokina, Jude Phillip, Paul Zumbo, Liron Yoffe, Paola Ghione, Anqi Wang, Xueshuai Han, Abigail Taylor, William Chiu, Valentina Fragliasso, Fabrizio Tabbo, Nahuel Zamponi, Nicolás Di Siervi, Clarisse Kayembe, Giovanni Medico, Ruchi P Patel, Marcello Gaudiano, Rodolfo Machiorlatti, Giuseppina Astone, Maria Teresa Cacciapuoti, Giorgia Zanetti, Claudia Pignataro, Ruiz Arvin Eric, Sanjay Patel, Francesca Zammarchi, Claudio Zanettini, Lucio Queiroz, Anastasia Nikitina, Olga Kudryashova, Anton Karelin, Daniil Nikitin, Dmitry Tychinin, Ekaterina Postovalova, Alexander Bagaev, Viktor Svekolkin, Ekaterina Belova, Katerina Tikhonova, Sandrine Degryse, Chengqi Xu, Domenico Novero, Maurilio Ponzoni, Enrico Tiacci, Brunangelo Falini, Joo Song, Inna Khodos, Elisa De Stanchina, Gabriele Macari, Luciana Cafforio, Simone Gardini, Roberto Piva, Enzo Medico, Samuel Y Ng, Allison Moskowitz, Zachary Epstein, Andrew Intlekofer, Dogan Ahmed, Wing C Chan, Peter Martin, Jia Ruan, Francesco Bertoni, Robin Foà, Joshua D Brody, David M Weinstock, Jaspreet Osan, Laura Santambrogio, Oliver Elemento, Doron Betel, Wayne Tam, Marco Ruella, Leandro Cerchietti, Raul Rabadan, Steven Horwitz, Giorgio Inghirami
{"title":"A patient-derived T cell lymphoma biorepository uncovers pathogenetic mechanisms and host-related therapeutic vulnerabilities.","authors":"Danilo Fiore, Luca Vincenzo Cappelli, Liu Zhaoqi, Nikita Kotlov, Maria Sorokina, Jude Phillip, Paul Zumbo, Liron Yoffe, Paola Ghione, Anqi Wang, Xueshuai Han, Abigail Taylor, William Chiu, Valentina Fragliasso, Fabrizio Tabbo, Nahuel Zamponi, Nicolás Di Siervi, Clarisse Kayembe, Giovanni Medico, Ruchi P Patel, Marcello Gaudiano, Rodolfo Machiorlatti, Giuseppina Astone, Maria Teresa Cacciapuoti, Giorgia Zanetti, Claudia Pignataro, Ruiz Arvin Eric, Sanjay Patel, Francesca Zammarchi, Claudio Zanettini, Lucio Queiroz, Anastasia Nikitina, Olga Kudryashova, Anton Karelin, Daniil Nikitin, Dmitry Tychinin, Ekaterina Postovalova, Alexander Bagaev, Viktor Svekolkin, Ekaterina Belova, Katerina Tikhonova, Sandrine Degryse, Chengqi Xu, Domenico Novero, Maurilio Ponzoni, Enrico Tiacci, Brunangelo Falini, Joo Song, Inna Khodos, Elisa De Stanchina, Gabriele Macari, Luciana Cafforio, Simone Gardini, Roberto Piva, Enzo Medico, Samuel Y Ng, Allison Moskowitz, Zachary Epstein, Andrew Intlekofer, Dogan Ahmed, Wing C Chan, Peter Martin, Jia Ruan, Francesco Bertoni, Robin Foà, Joshua D Brody, David M Weinstock, Jaspreet Osan, Laura Santambrogio, Oliver Elemento, Doron Betel, Wayne Tam, Marco Ruella, Leandro Cerchietti, Raul Rabadan, Steven Horwitz, Giorgio Inghirami","doi":"10.1016/j.xcrm.2025.102029","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102029","url":null,"abstract":"<p><p>Peripheral T cell lymphomas (PTCLs) comprise heterogeneous malignancies with limited therapeutic options. To uncover targetable vulnerabilities, we generate a collection of PTCL patient-derived tumor xenografts (PDXs) retaining histomorphology and molecular donor-tumor features over serial xenografting. PDX demonstrates remarkable heterogeneity, complex intratumor architecture, and stepwise trajectories mimicking primary evolutions. Combining functional transcriptional stratification and multiparametric imaging, we identify four distinct PTCL microenvironment subtypes with prognostic value. Mechanistically, we discover a subset of PTCLs expressing Epstein-Barr virus-specific T cell receptors and uncover the capacity of cancer-associated fibroblasts of counteracting treatments. PDXs' pre-clinical testing captures individual vulnerabilities, mirrors donor patients' clinical responses, and defines effective patient-tailored treatments. Ultimately, we assess the efficacy of CD5KO- and CD30- Chimeric Antigen Receptor T Cells (CD5KO-CART and CD30_CART, respectively), demonstrating their therapeutic potential and the synergistic role of immune checkpoint inhibitors for PTCL treatment. This repository represents a resource for discovering and validating intrinsic and extrinsic factors and improving the selection of drugs/combinations and immune-based therapies.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102029"},"PeriodicalIF":11.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728544","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
Radioimmunotherapy for peritoneal carcinomatosis: Preclinical proof of concept to clinical translation. 腹膜癌的放射免疫治疗:从概念到临床转化的临床前证明。
IF 11.7 1区 医学
Cell Reports Medicine Pub Date : 2025-03-24 DOI: 10.1016/j.xcrm.2025.102040
Nicole Aguirre, Darren R Veach, Andrea Cercek, Sarah M Cheal, Steven M Larson, Garrett M Nash, Nai-Kong V Cheung
{"title":"Radioimmunotherapy for peritoneal carcinomatosis: Preclinical proof of concept to clinical translation.","authors":"Nicole Aguirre, Darren R Veach, Andrea Cercek, Sarah M Cheal, Steven M Larson, Garrett M Nash, Nai-Kong V Cheung","doi":"10.1016/j.xcrm.2025.102040","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102040","url":null,"abstract":"<p><p>Peritoneal carcinomatosis (PC), characterized by the dissemination of metastatic tumor cells throughout the peritoneal cavity from several gastrointestinal and gynecological malignancies, has significantly compromised patient survival. The standard of care is cytoreductive surgery with or without intraperitoneal chemotherapy. However, surgical resection often leaves behind microscopic or clinically occult disease due to the complex anatomy of the peritoneum, where intraperitoneal chemotherapy and systemic chemotherapy have shown limited success. To improve the therapeutic outcome, targeted therapy using radionuclides such as alpha, beta, and Auger emitters delivered by antibodies is actively being investigated. While preclinical murine models of PC have shown the potential of radioimmunotherapy (RIT) using various radioisotopes across a wide spectrum of antigen targets and tumor diagnoses with acceptable toxicities, successful clinical trials are lacking. Here, we retrospectively summarize preclinical and clinical PC studies, consider their translational potential, and examine paths to development that maximize the clinical benefit of RIT in this context.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102040"},"PeriodicalIF":11.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742406","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
Single-cut gene therapy in a one-step generated rhesus monkey model of Duchenne muscular dystrophy. 一步生成的恒河猴杜氏肌营养不良模型的单切口基因治疗。
IF 11.7 1区 医学
Cell Reports Medicine Pub Date : 2025-03-24 DOI: 10.1016/j.xcrm.2025.102037
Raoxian Bai, Wenting Guo, Ting Zhang, Shuaiwei Ren, Jie Liu, Puhao Xiao, Junyu Zhang, Wenjie Sun, Jiao Yang, Yue Ma, Siyu Liu, Chaoran Zhou, Shangang Li, Hong Wang, Shu Zhang, Weizhi Ji, Shiwen Wu, Yongchang Chen
{"title":"Single-cut gene therapy in a one-step generated rhesus monkey model of Duchenne muscular dystrophy.","authors":"Raoxian Bai, Wenting Guo, Ting Zhang, Shuaiwei Ren, Jie Liu, Puhao Xiao, Junyu Zhang, Wenjie Sun, Jiao Yang, Yue Ma, Siyu Liu, Chaoran Zhou, Shangang Li, Hong Wang, Shu Zhang, Weizhi Ji, Shiwen Wu, Yongchang Chen","doi":"10.1016/j.xcrm.2025.102037","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102037","url":null,"abstract":"<p><p>Progress in Duchenne muscular dystrophy (DMD) treatment is hindered by the lack of animal models that closely replicate human pathology and enable the evaluation of therapy efficacy and safety based on these models. To address this need, we optimize the generation of nonhuman primate DMD models, reducing the development time from 6 to 7 years to under 1 year, enabling the rapid generation of DMD monkey models. These models closely mimic human DMD pathology and motor dysfunction, making them suitable for testing gene therapies. Using these models, we develop a single-cut gene therapy strategy that can be directly applied to humans. This treatment restores dystrophin expression, improves pathological features, and enhances motor abilities in DMD monkeys, with effects lasting at least 1.5 years. In conclusion, we achieve the rapid generation of DMD monkey models and demonstrate that our gene therapy approach is effective and holds significant potential for clinical application.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102037"},"PeriodicalIF":11.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728757","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
Inhibition of basal IL-6 activity promotes subcutaneous fat retention in humans during fasting and postprandial states. 抑制基础IL-6活性促进人类在禁食和餐后状态下皮下脂肪潴留。
IF 11.7 1区 医学
Cell Reports Medicine Pub Date : 2025-03-22 DOI: 10.1016/j.xcrm.2025.102042
Beckey Trinh, Signe Johanne Rasmussen, Mathilde Ehnhuus Brøgger-Jensen, Christoph Andreas Engelhard, Anton Lund, Ana Rita Tavanez, Alexandra Vassilieva, Susanne Janum, Ulrik Winning Iepsen, Bente Kiens, Kirsten Møller, Bente Klarlund Pedersen, Gerrit Van Hall, Helga Ellingsgaard
{"title":"Inhibition of basal IL-6 activity promotes subcutaneous fat retention in humans during fasting and postprandial states.","authors":"Beckey Trinh, Signe Johanne Rasmussen, Mathilde Ehnhuus Brøgger-Jensen, Christoph Andreas Engelhard, Anton Lund, Ana Rita Tavanez, Alexandra Vassilieva, Susanne Janum, Ulrik Winning Iepsen, Bente Kiens, Kirsten Møller, Bente Klarlund Pedersen, Gerrit Van Hall, Helga Ellingsgaard","doi":"10.1016/j.xcrm.2025.102042","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102042","url":null,"abstract":"<p><p>Interleukin-6 (IL-6) knockout mice and humans treated with IL-6 receptor blockade gain adipose tissue mass. This study investigates whether basal IL-6 activity (resting IL-6 levels) influences fat storage during fasting and postprandial states. Using stable-isotope tracer techniques and IL-6 receptor blockade with tocilizumab, we examine fat kinetics in humans. Blocking basal IL-6 activity reduces fasting whole-body lipolysis, decreases hormone-sensitive lipase (HSL) phosphorylation and fatty acid release in adipose tissue, and impairs postprandial fatty acid uptake in the leg. These results suggest diminished fatty acid uptake and oxidation in skeletal muscle, along with enhanced fatty acid entrapment in adipose tissue, which may account for the increased adiposity in the absence of IL-6 activity. Additionally, IL-6 blockade increases the escape of meal-derived fatty acids into the bloodstream. Whether this affects fatty acid storage and lipotoxicity in other tissues warrants further investigation. This study was registered at ClinicalTrials.gov (NCT04687540).</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102042"},"PeriodicalIF":11.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728723","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
A spatially resolved transcriptome landscape during thyroid cancer progression. 甲状腺癌进展期间的空间分解转录组景观。
IF 11.7 1区 医学
Cell Reports Medicine Pub Date : 2025-03-20 DOI: 10.1016/j.xcrm.2025.102043
Tian Liao, Yu Zeng, Weibo Xu, Xiao Shi, Cenkai Shen, Yuxin Du, Meng Zhang, Yan Zhang, Ling Li, Peipei Ding, Weiguo Hu, Zhiheng Huang, Man Him Matrix Fung, Qinghai Ji, Yu Wang, Shengli Li, Wenjun Wei
{"title":"A spatially resolved transcriptome landscape during thyroid cancer progression.","authors":"Tian Liao, Yu Zeng, Weibo Xu, Xiao Shi, Cenkai Shen, Yuxin Du, Meng Zhang, Yan Zhang, Ling Li, Peipei Ding, Weiguo Hu, Zhiheng Huang, Man Him Matrix Fung, Qinghai Ji, Yu Wang, Shengli Li, Wenjun Wei","doi":"10.1016/j.xcrm.2025.102043","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102043","url":null,"abstract":"<p><p>Tumor microenvironment (TME) remodeling plays a pivotal role in thyroid cancer progression, yet its spatial dynamics remain unclear. In this study, we integrate spatial transcriptomics and single-cell RNA sequencing to map the TME architecture across para-tumor thyroid (PT) tissue, papillary thyroid cancer (PTC), locally advanced PTC (LPTC), and anaplastic thyroid carcinoma (ATC). Our integrative analysis reveals extensive molecular and cellular heterogeneity during thyroid cancer progression, enabling the identification of three distinct thyrocyte meta-clusters, including TG<sup>+</sup>IYG<sup>+</sup> subpopulation in PT, HLA-DRB1<sup>+</sup>HLA-DRA<sup>+</sup> subpopulation in early cancerous stages, and APOE<sup>+</sup>APOC1<sup>+</sup> subpopulation in late-stage progression. We reveal stage-specific tumor leading edge remodeling and establish high-confidence cell-cell interactions, such as COL8A1-ITHB1 in PTC, LAMB2-ITGB4 in LPTC, and SERPINE1-PLAUR in ATC. Notably, both SERPINE1 expression level and SERPINE1<sup>+</sup> fibroblast abundance correlate with malignant progression and prognosis. These findings provide a spatially resolved framework of TME remodeling, offering insights for thyroid cancer diagnosis and treatment.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102043"},"PeriodicalIF":11.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742398","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
Screening of patient-derived organoids identifies mitophagy as a cell-intrinsic vulnerability in colorectal cancer during statin treatment. 筛选患者来源的类器官确定有丝自噬是他汀类药物治疗期间结直肠癌的细胞固有脆弱性。
IF 11.7 1区 医学
Cell Reports Medicine Pub Date : 2025-03-19 DOI: 10.1016/j.xcrm.2025.102039
Zhi-Hang Tao, Ji-Xuan Han, Jia Xu, Enhao Zhao, Ming Wang, Zheng Wang, Xiao-Lin Lin, Xiu-Ying Xiao, Jie Hong, Haoyan Chen, Ying-Xuan Chen, Hui-Min Chen, Jing-Yuan Fang
{"title":"Screening of patient-derived organoids identifies mitophagy as a cell-intrinsic vulnerability in colorectal cancer during statin treatment.","authors":"Zhi-Hang Tao, Ji-Xuan Han, Jia Xu, Enhao Zhao, Ming Wang, Zheng Wang, Xiao-Lin Lin, Xiu-Ying Xiao, Jie Hong, Haoyan Chen, Ying-Xuan Chen, Hui-Min Chen, Jing-Yuan Fang","doi":"10.1016/j.xcrm.2025.102039","DOIUrl":"https://doi.org/10.1016/j.xcrm.2025.102039","url":null,"abstract":"<p><p>Statins, commonly used to lower cholesterol, are associated with improved prognosis in colorectal cancer (CRC), though their effectiveness varies. This study investigates the anti-cancer effects of atorvastatin in CRC using patient-derived organoids (PDOs) and PDO-derived xenograft (PDOX) models. Our findings reveal that atorvastatin induces mitochondrial dysfunction, leading to apoptosis in cancer cells. In response, cancer cells induce mitophagy to clear damaged mitochondria, enhancing survival and reducing statin efficacy. Analysis of a clinical cohort confirms mitophagy's role in diminishing statin effectiveness. Importantly, inhibiting mitophagy significantly enhances the anti-cancer effects of atorvastatin in CRC PDOs, xenograft models, and azoxymethane (AOM)-dextran sulfate sodium (DSS) mouse models. These findings identify mitophagy as a critical pro-survival mechanism in CRC during statin treatment, providing insights into the variable responses observed in epidemiological studies. Targeting this vulnerability through combination therapy can elicit potent therapeutic responses.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102039"},"PeriodicalIF":11.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742326","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
Interferon-γ-stimulated antigen-presenting cancer-associated fibroblasts hinder neoadjuvant chemoimmunotherapy efficacy in lung cancer. 干扰素γ刺激抗原呈递癌相关成纤维细胞阻碍肺癌新辅助化疗免疫治疗的疗效。
IF 11.7 1区 医学
Cell Reports Medicine Pub Date : 2025-03-18 Epub Date: 2025-03-07 DOI: 10.1016/j.xcrm.2025.102017
Zhengqi Cao, Zhouwenli Meng, Jian Li, Yu Tian, Li Lu, Anni Wang, Jia Huang, Jingze Wang, Jing Sun, Lixuan Chen, Shun Lu, Ziming Li
{"title":"Interferon-γ-stimulated antigen-presenting cancer-associated fibroblasts hinder neoadjuvant chemoimmunotherapy efficacy in lung cancer.","authors":"Zhengqi Cao, Zhouwenli Meng, Jian Li, Yu Tian, Li Lu, Anni Wang, Jia Huang, Jingze Wang, Jing Sun, Lixuan Chen, Shun Lu, Ziming Li","doi":"10.1016/j.xcrm.2025.102017","DOIUrl":"10.1016/j.xcrm.2025.102017","url":null,"abstract":"<p><p>Conventional neoadjuvant chemotherapy provides limited benefit for patients with resectable non-small cell lung cancer (NSCLC). Recently, neoadjuvant chemoimmunotherapy (NCIT) has transformed the perioperative management of NSCLC by priming systemic anti-tumor immunity before surgery, yet it remains ineffective for at least 50% of patients. Through single-cell sequencing analysis of our NCIT cohort, we identify that antigen-presenting cancer-associated fibroblasts (apCAFs) can impede the efficacy of NCIT. Using a custom cancer-associated fibroblast biobank, we uncover that interferon (IFN)-γ stimulates apCAF expansion via the JAK1/2-STAT1-IFI6/27 pathway. Mechanistically, apCAFs significantly contribute to PD-L2 expression in the tumor microenvironment (TME), triggering the accumulation of FOXP1<sup>+</sup>regulatory T cells (Tregs) through the PD-L2-RGMB axis. Reprogramming apCAFs by inhibiting the IFN-γ pathway or blocking the PD-L2-RGMB axis substantially mitigates apCAFs-mediated FOXP1<sup>+</sup>Tregs' expansion. In summary, we reveal the role of apCAFs in compromising NCIT efficacy and propose applications for anti-PD-L2/RGMB regimens to synergize with anti-PD1 therapies by targeting apCAFs.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102017"},"PeriodicalIF":11.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584935","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
Engineered human myogenic cells in hydrogels generate innervated vascularized myofibers within dystrophic mouse muscle on long-term engraftment. 水凝胶中工程化的人成肌细胞在营养不良小鼠肌肉中长期移植产生神经支配的血管化肌纤维。
IF 11.7 1区 医学
Cell Reports Medicine Pub Date : 2025-03-18 Epub Date: 2025-03-07 DOI: 10.1016/j.xcrm.2025.102019
Anna Kowala, James Boot, Jinhong Meng, Charles A Mein, Olivier Pourquié, John T Connelly, Jennifer E Morgan, Yung-Yao Lin
{"title":"Engineered human myogenic cells in hydrogels generate innervated vascularized myofibers within dystrophic mouse muscle on long-term engraftment.","authors":"Anna Kowala, James Boot, Jinhong Meng, Charles A Mein, Olivier Pourquié, John T Connelly, Jennifer E Morgan, Yung-Yao Lin","doi":"10.1016/j.xcrm.2025.102019","DOIUrl":"10.1016/j.xcrm.2025.102019","url":null,"abstract":"<p><p>Transplantation of human myogenic progenitor cells (MPCs) is a promising therapeutic strategy for treating muscle-wasting diseases, e.g., Duchenne muscular dystrophy (DMD). To increase engraftment efficiency of donor stem cells, modulation of host muscles is required, significantly limiting their clinical translation. Here, we develop a clinically relevant transplantation strategy synergizing hydrogel-mediated delivery and engineered human MPCs generated from CRISPR-corrected DMD patient-derived pluripotent stem cells. We demonstrate that donor-derived human myofibers produce full-length dystrophin at 4 weeks and 5-6 months (long-term) after transplantation in the unmodulated muscles of the dystrophin-deficient mouse model of DMD. Remarkably, human myofibers are innervated by mouse motor neurons forming neuromuscular junctions and supported by vascularization after long-term engraftment in dystrophic mice. PAX7+ cells of human origin populate the satellite cell niche. There was no evidence of tumorigenesis in mice engrafted with hydrogel-encapsulated human MPCs. Our results provide a proof of concept in developing hydrogel-based cell therapy for muscle-wasting diseases.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"102019"},"PeriodicalIF":11.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584934","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
Assessments of lung nodules by an artificial intelligence chatbot using longitudinal CT images. 利用纵向CT图像的人工智能聊天机器人评估肺结节。
IF 11.7 1区 医学
Cell Reports Medicine Pub Date : 2025-03-18 Epub Date: 2025-03-04 DOI: 10.1016/j.xcrm.2025.101988
Yuqiang Mao, Nan Xu, Yanan Wu, Lu Wang, Hongtao Wang, Qianqian He, Tianqi Zhao, Shuangchun Ma, Meihong Zhou, Hongjie Jin, Dongmei Pei, Lina Zhang, Jiangdian Song
{"title":"Assessments of lung nodules by an artificial intelligence chatbot using longitudinal CT images.","authors":"Yuqiang Mao, Nan Xu, Yanan Wu, Lu Wang, Hongtao Wang, Qianqian He, Tianqi Zhao, Shuangchun Ma, Meihong Zhou, Hongjie Jin, Dongmei Pei, Lina Zhang, Jiangdian Song","doi":"10.1016/j.xcrm.2025.101988","DOIUrl":"10.1016/j.xcrm.2025.101988","url":null,"abstract":"<p><p>Large language models have shown efficacy across multiple medical tasks. However, their value in the assessment of longitudinal follow-up computed tomography (CT) images of patients with lung nodules is unclear. In this study, we evaluate the ability of the latest generative pre-trained transformer (GPT)-4o model to assess changes in malignancy probability, size, and features of lung nodules on longitudinal CT scans from 647 patients (547 from two local centers and 100 from a public dataset). GPT-4o achieves an average accuracy of 0.88 in predicting lung nodule malignancy compared to pathological results and an average intraclass correlation coefficient of 0.91 in measuring nodule size compared with manual measurements by radiologists. Six radiologists' evaluations demonstrate GPT-4o's ability to capture changes in nodule features with a median Likert score of 4.17 (out of 5.00). In summary, GPT-4o could capture dynamic changes in lung nodules across longitudinal follow-up CT images, thus providing high-quality radiological evidence to assist in clinical management.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101988"},"PeriodicalIF":11.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566268","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
Outer radial glia promotes white matter regeneration after neonatal brain injury. 外放射状胶质细胞促进新生儿脑损伤后白质再生。
IF 11.7 1区 医学
Cell Reports Medicine Pub Date : 2025-03-18 Epub Date: 2025-02-28 DOI: 10.1016/j.xcrm.2025.101986
Hideo Jinnou, Lauren M Rosko, Satoshi Yamashita, Soichiro Henmi, Jaya Prasad, Van K Lam, Artur Agaronyan, Tsang-Wei Tu, Yuka Imamura, Kazuya Kuboyama, Kazunobu Sawamoto, Kazue Hashimoto-Torii, Nobuyuki Ishibashi, Vittorio Gallo
{"title":"Outer radial glia promotes white matter regeneration after neonatal brain injury.","authors":"Hideo Jinnou, Lauren M Rosko, Satoshi Yamashita, Soichiro Henmi, Jaya Prasad, Van K Lam, Artur Agaronyan, Tsang-Wei Tu, Yuka Imamura, Kazuya Kuboyama, Kazunobu Sawamoto, Kazue Hashimoto-Torii, Nobuyuki Ishibashi, Vittorio Gallo","doi":"10.1016/j.xcrm.2025.101986","DOIUrl":"10.1016/j.xcrm.2025.101986","url":null,"abstract":"<p><p>The developing gyrencephalic brain contains a large population of neural stem cells in the ventricular zone and outer subventricular zone (OSVZ), the latter populated by outer radial glia (oRG). The role of oRG during postnatal development is not well understood. We show that oRG cells increase proliferative capacity and contribute to oligodendrocyte precursor cell (OPC) production following brain injury in human infants and neonatal piglets, whose brains resemble the human brain in structure and development. RNA sequencing revealed oRG-specific transcriptional responses to injury in piglets and showed that the activating transcription factor 5 (ATF5) pathway positively regulates oRG proliferation. Intranasal activation of ATF5 using salubrinal enhanced OSVZ-derived oligodendrogenesis in the injured periventricular white matter and improved functional recovery. These results reveal a key role for postnatal oRG in brain injury recovery and identify ATF5 as a potential therapeutic target for treating white matter injury in infants.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101986"},"PeriodicalIF":11.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536773","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}
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