Disease Models & Mechanisms最新文献_第7页

Enhancing the in vitro architecture of human disease. 增强人类疾病的体外结构。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-06-01 Epub Date: 2026-07-09 DOI: 10.1242/dmm.053091

Kirsty Hooper, Dina Mikimoto, Vivian Li, Austin Smith, Joseph Wu

引用次数: 0

Hyperpolarised magnetic resonance spectroscopy with lab-on-a-chip disease models. 超极化磁共振波谱与芯片实验室疾病模型。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-06-01 Epub Date: 2026-07-08 DOI: 10.1242/dmm.052817

Irene Marco-Rius, Pernille Rose Jensen, Lotte Bonde Bertelsen

{"title":"Hyperpolarised magnetic resonance spectroscopy with lab-on-a-chip disease models.","authors":"Irene Marco-Rius, Pernille Rose Jensen, Lotte Bonde Bertelsen","doi":"10.1242/dmm.052817","DOIUrl":"10.1242/dmm.052817","url":null,"abstract":"Hyperpolarised magnetic resonance spectroscopy (HP-MRS) enables real-time, non-invasive assessment of metabolism by increasing signal sensitivity by more than four orders of magnitude compared with conventional magnetic resonance spectroscopy (MRS). This signal enhancement is achieved by preparing nuclear spin populations in a non-equilibrium state prior to measurement, generating a substrate with a transient strongly amplified signal that enables detection of rapid metabolic conversion in real time. Integration of HP-MRS with cell-based microfluidic disease models (engineered systems in which living cells are cultured within controlled microscale environments that mimic key aspects of tissue physiology) enables dynamic metabolic profiling in physiologically relevant settings. These models are typically implemented as organ-on-a-chip platforms, where microfabricated channels enable precise control over perfusion, nutrient delivery, oxygenation and cellular interactions. Combined HP-MRS and chip-based microfluidic platforms enable direct, non-destructive assessment of metabolic transformations, with applications in biomarker discovery, treatment response assessment and personalised medicine. This At a Glance article reviews recent advances in chip-based microfluidic systems that are integrated with HP-MRS platforms, including designs compatible with benchtop and high-field nuclear magnetic resonance systems together with clinical magnetic resonance imaging systems. Key challenges for this technology include constraints imposed by signal decay time, variability in polarisation levels, injection reproducibility and the lack of standardised data processing.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"19 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13382991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Disease modelling with in vitro vascularised organoids. 用体外血管化类器官建立疾病模型。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-06-01 Epub Date: 2026-05-20 DOI: 10.1242/dmm.052769

Chloe Kan, Lu Liu, Rio Sugimura

引用次数: 0

Human induced pluripotent stem cell-derived inner ear organoids reveal hair cell damage and plasticity after cisplatin and gentamicin exposure. 顺铂和庆大霉素暴露后，人诱导多能干细胞衍生的内耳类器官显示毛细胞损伤和可塑性。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-06-01 Epub Date: 2026-03-03 DOI: 10.1242/dmm.052511

Amy W A Lucassen, Winnie M C van den Boogaard, Esther Fousert, Jingyuan Zhang, Karl R Koehler, John C M J de Groot, Peter Paul G van Benthem, Wouter H van der Valk, Heiko Locher

{"title":"Human induced pluripotent stem cell-derived inner ear organoids reveal hair cell damage and plasticity after cisplatin and gentamicin exposure.","authors":"Amy W A Lucassen, Winnie M C van den Boogaard, Esther Fousert, Jingyuan Zhang, Karl R Koehler, John C M J de Groot, Peter Paul G van Benthem, Wouter H van der Valk, Heiko Locher","doi":"10.1242/dmm.052511","DOIUrl":"10.1242/dmm.052511","url":null,"abstract":"Ototoxicity is a leading cause of sensory deficits, including hearing loss and balance disorders. Predicting ototoxicity is challenging owing to translatability issues of animal models and limited access to human inner ear tissue. Known ototoxic drugs, such as cisplatin (a chemotherapeutic) and gentamicin (an aminoglycoside antibiotic), cause irreversible damage to sensory hair cells and neurons. Here, we establish human induced pluripotent stem cell (hiPSC)-derived inner ear organoids as an in vitro model for studying ototoxicity. Exposure to cisplatin and gentamicin led to hair cell and neuronal loss, disrupted organoid architecture and increased cell damage, including apoptosis, in a dose-dependent manner. Remarkably, prolonged culture of treated organoids showed re-emergence of otic vesicle structures with sensory hair cells and neurons. SOX10+ otic epithelial cells exhibited increased Ki-67 expression, indicating a potential for developmental plasticity. Our findings demonstrate the value of hiPSC-derived inner ear organoids as a platform for human ototoxicity modeling and provide a basis for testing otoprotective interventions, offering insights into the intrinsic plasticity of developing inner ear cells.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"19 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12994450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 3D lymph node model for chronic lymphocytic leukaemia recapitulates microenvironmental features and drug response in vitro. 慢性淋巴细胞白血病的三维淋巴结模型概括了体外微环境特征和药物反应。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-06-01 Epub Date: 2026-03-31 DOI: 10.1242/dmm.052731

Daniela Belloni, Dafne Barozzi, Giulia Milani, Federica Barbaglio, Aswin Raj Puthukkunnath, Pamela Ranghetti, Eleonora Perotta, Teresa Musco, Marta Sampietro, Maurilio Ponzoni, Lydia Scarfò, Paolo Ghia, Cristina Scielzo

{"title":"A 3D lymph node model for chronic lymphocytic leukaemia recapitulates microenvironmental features and drug response in vitro.","authors":"Daniela Belloni, Dafne Barozzi, Giulia Milani, Federica Barbaglio, Aswin Raj Puthukkunnath, Pamela Ranghetti, Eleonora Perotta, Teresa Musco, Marta Sampietro, Maurilio Ponzoni, Lydia Scarfò, Paolo Ghia, Cristina Scielzo","doi":"10.1242/dmm.052731","DOIUrl":"10.1242/dmm.052731","url":null,"abstract":"Chronic lymphocytic leukaemia (CLL) cells circulate between the blood, bone marrow (BM) and lymphoid organs, where interactions with the lymph node (LN) microenvironment enhance their survival, proliferation and drug resistance. Most in vitro models fail to reproduce the spatial and cellular complexity of the LN niche, limiting studies of tissue-specific drug responses. To address this, we developed a 3D LN model using a gelatine scaffold and a clinorotator bioreactor previously validated for a BM system. The scaffold was seeded with human lymphatic fibroblasts and endothelial cells, which deposited extracellular matrix and supported patient-derived CLL cell viability and proliferation. Consistent with in vivo observations, CLL cells within the scaffold downregulated the chemokine receptor CXCR4, further reduced upon proliferative stimulation. Final validation involved treatment with targeted therapies: the BCL-2 antagonist venetoclax and the BTK inhibitor ibrutinib. Venetoclax treatment revealed greater CLL protection within the LN environment than in BM, whereas the mobilizing effect of ibrutinib was comparable between these two niches. This 3D LN model offers an effective ex vivo platform for studying microenvironment-tumour interactions and tissue-specific drug responses.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13072081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Myeloperoxidase impairs mucociliary transport on human airway epithelium. 髓过氧化物酶损害人气道上皮粘膜纤毛运输。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-06-01 Epub Date: 2026-05-26 DOI: 10.1242/dmm.052764

Allison Boboltz, Vaidehi Rathi, Sahana Kumar, Gregg A Duncan

{"title":"Myeloperoxidase impairs mucociliary transport on human airway epithelium.","authors":"Allison Boboltz, Vaidehi Rathi, Sahana Kumar, Gregg A Duncan","doi":"10.1242/dmm.052764","DOIUrl":"10.1242/dmm.052764","url":null,"abstract":"Dampening neutrophil-driven inflammation in the airways remains a challenge in treating cystic fibrosis (CF) lung disease. Myeloperoxidase (MPO) is a neutrophilic enzyme that produces reactive oxygen species and is highly concentrated in CF airways. Greater MPO concentrations have previously been correlated with increased mucus plugging in bronchiectasis, suggesting that MPO could impair mucociliary transport. As such, we evaluated the impact of MPO treatment on barrier integrity, mucin production, mucus viscoelasticity and mucociliary transport in fully differentiated human airway epithelial cultures at ionic conditions reflective of healthy and CF-affected airways. Using live-cell imaging and particle velocimetry, we found that MPO inhibits mucociliary transport in vitro at CF-like and normal airway conditions. The impairment of mucus clearance by MPO was similar to that by neutrophil elastase, another neutrophilic granular enzyme that damages the host tissues and impairs airway clearance. We also found that subsequent treatment with the reducing agent, N-acetyl cysteine, could alleviate MPO-mediated mucociliary dysfunction through disulfide bond cleavage. These findings identify MPO as a therapeutic target to resolve deficits in airway clearance function in CF and related muco-obstructive lung diseases.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13267771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Induced pluripotent stem cells from a transgenic minipig model of Huntington's disease reveal early metabolic changes. 从亨廷顿氏病转基因迷你猪模型中诱导的多能干细胞揭示了早期代谢变化。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-06-01 Epub Date: 2026-05-11 DOI: 10.1242/dmm.052585

Irena Rysankova, David Sekac, Hana Hansikova, Katerina Vodickova Kepkova, Petr Vodicka, Michaela Vaskovicova, Marie Altmanova, Stefan Juhas, Jana Juhasova, Eliska Taborska, Jiri Klempir, Jan Motlik, Jiri Klima, Lars Eide, Zdenka Ellederova

{"title":"Induced pluripotent stem cells from a transgenic minipig model of Huntington's disease reveal early metabolic changes.","authors":"Irena Rysankova, David Sekac, Hana Hansikova, Katerina Vodickova Kepkova, Petr Vodicka, Michaela Vaskovicova, Marie Altmanova, Stefan Juhas, Jana Juhasova, Eliska Taborska, Jiri Klempir, Jan Motlik, Jiri Klima, Lars Eide, Zdenka Ellederova","doi":"10.1242/dmm.052585","DOIUrl":"10.1242/dmm.052585","url":null,"abstract":"Huntington's disease (HD) is a neurodegenerative autosomal dominant hereditary disease caused by a CAG triplet repeat expansion mutation in the gene encoding the huntingtin (HTT) protein. The main feature of HD is the loss of striatal neurons, accompanied by metabolic and transcriptional alterations in both neural and peripheral tissues. Induced pluripotent stem cells (iPSCs) derived from a transgenic HD (TgHD) minipig model expressing a mutant HTT construct were generated to investigate early metabolic, antioxidant and DNA integrity changes associated with HD development. Gene expression analysis showed increased expression of vascular endothelial growth factor (VEGF), pyruvate dehydrogenase kinase 1 (PDK1) and glutamine-oxaloacetic transaminase 1 (GOT1), implying early metabolic alteration in TgHD iPSCs. Moreover, upregulated FANCD2/FANCI-associated nuclease 1 (FAN1) expression indicated genotoxic stress linked to early HD development. These findings suggest metabolic shifts and putative genotoxic events in the pluripotent stem cell state of the TgHD model and point to early effect of the HD mutation. The model may be suitable for evaluating potential cell therapy and in vitro differentiation of iPSCs to neurons and other cells affected in HD.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"19 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Leveraging organoid models to understand mechanisms of viral infections and immunity in bats. 利用类器官模型来了解蝙蝠的病毒感染和免疫机制。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-06-01 Epub Date: 2026-05-13 DOI: 10.1242/dmm.052737

Shelby R Madden, Agnieszka Rynda-Apple, Diane Bimczok

{"title":"Leveraging organoid models to understand mechanisms of viral infections and immunity in bats.","authors":"Shelby R Madden, Agnieszka Rynda-Apple, Diane Bimczok","doi":"10.1242/dmm.052737","DOIUrl":"10.1242/dmm.052737","url":null,"abstract":"Bats are important reservoir hosts for zoonotic viruses owing to their unusual ability to avoid development of clinical disease and pathological lesions upon viral infection. Research efforts to understand the unique responses of bats to viral infection have been limited by the vast number of bat species and the lack of accessible experimental model systems. Over the past 5 years, organoid models, which are long-term cultures of primary cells, have been developed from gastrointestinal, respiratory and kidney tissues of multiple fruit-eating and insectivorous bats. Compared with human organoids, bat organoids showed increased expression of type I and type III interferon genes, other antiviral genes and complement genes at baseline and in response to viral stimulation. Bat organoids generally showed strong upregulation of interferon genes and interferon-stimulated genes in response to viruses. Conversely, the ability of bat organoids to support viral replication was dependent on the virus, tissue type and bat species. Overall, the recent progress in the field demonstrates the potential of organoids to serve as relevant models for exploring species- and tissue-specific responses to viruses in bats.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"19 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

In vitro and in vivo models for androgenetic alopecia drug development. 雄激素性脱发体外和体内模型的药物开发。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-06-01 Epub Date: 2026-07-08 DOI: 10.1242/dmm.052848

Shan Tu, Ayaka Nanmo, Yuki Migita, Tomoki Asaba, Jieun Seo, Sayuri Hamano, Tatsuto Kageyama, Junji Fukuda

{"title":"In vitro and in vivo models for androgenetic alopecia drug development.","authors":"Shan Tu, Ayaka Nanmo, Yuki Migita, Tomoki Asaba, Jieun Seo, Sayuri Hamano, Tatsuto Kageyama, Junji Fukuda","doi":"10.1242/dmm.052848","DOIUrl":"10.1242/dmm.052848","url":null,"abstract":"Alopecia is a common disorder that can cause hair loss owing to various factors, including genetics, stress and diet. Androgenetic alopecia (AGA), also known as male pattern baldness, is the most common type of progressive hair loss. AGA symptoms can be alleviated by effective drugs, such as finasteride and minoxidil. Therefore, most patients with alopecia select drug therapy as the first-line treatment. However, their side effects and variable efficacy have increased the demand for alternative treatment options for these patients. Despite the high clinical demand, the development of novel therapeutic agents remains limited, primarily due to the lack of physiologically relevant drug testing models that accurately predict drug effects in humans. In this At a Glance article, we provide an overview of the currently available in vitro models for hair drug testing. First, we outline the limitations of traditional models, such as two-dimensional cultures and animal models, in reproducing hair follicle structures and multicellular signaling pathways. We then introduce three-dimensional culture platforms that partially overcome these drawbacks. Next, we discuss the differences and applications of various models in terms of functional readouts, reproducibility, high-throughput potential, standardization and cost. We highlight recent progress in the development of follicular skin model constructs and propose practical metrics for selecting the most appropriate model for the initial screening of potential hair drugs. Overall, this At a Glance article provides a roadmap towards a more translationally valuable screening system for the discovery and development of hair loss treatments.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"19 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13382705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Mesoscale maladaptation in disease organoids. 疾病类器官的中尺度适应失调。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-06-01 Epub Date: 2026-06-29 DOI: 10.1242/dmm.052951

Masashi Okamoto, Takanori Takebe

{"title":"Mesoscale maladaptation in disease organoids.","authors":"Masashi Okamoto, Takanori Takebe","doi":"10.1242/dmm.052951","DOIUrl":"10.1242/dmm.052951","url":null,"abstract":"In chronic diseases, multiple tissue components at a shared interface often deteriorate concurrently, and disease progression may depend on interactions among these failures rather than on any single defect. Multi-tissue organoid models can mimic disease-relevant pathology in vitro, but the field lacks a simple framework for comprehensive interrogation. Here, we propose mesoscale maladaptation as an operational concept for multi-tissue disease modelling, defined as a synergistic decline in interdependent functions that can occur between two or more tissue elements. To detect maladaptation, we introduce a stepwise workflow that identifies the failing tissue elements, defines directionality of potential interdependence between these elements and compares combined perturbations with single perturbations to evaluate synergistic decline. We apply this framework to intestinal neuromuscular, hepatic sinusoidal, blood-brain barrier and tumour-neural interfaces, but it can be extrapolated to other organs and systems. This framework will illuminate future directions for in vitro complex disease modelling by enriching biological insights to disentangle progressive pathology, shifting the focus from localised biological failures to concurrent multi-tissue failures that produce synergistic pathology.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"19 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13382832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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