In vitro models最新文献

{"title":"3D in vitro co-culture disc for assessing cancer invasiveness in the tumor stroma microenvironment.","authors":"Weiyou Sun, Yutaka Kikuchi, Haruko Takahashi","doi":"10.1007/s44164-026-00106-0","DOIUrl":"https://doi.org/10.1007/s44164-026-00106-0","url":null,"abstract":"<p><strong>Purpose: </strong>Cancer cell invasion into the stroma is a key step in tumor progression, yet many in vitro models fail to recapitulate stromal architecture or permit quantitative analysis along the thickness (Z) dimension. This study aimed to develop a simple 3D co-culture disc system that maintains fibroblast-rich gels without shrinkage and enables quantitative evaluation of epithelial cancer cell invasion.</p><p><strong>Methods: </strong>A thin plastic disc with a central opening was used to support collagen gels containing normal human lung fibroblasts (NHLFs). Noncancerous MCF-10 A and cancer cell lines with different invasive capacities (MCF-7, MDA-MB-231) were seeded on the gel surface. Gel contraction, fibroblast morphology, and invasion depth were assessed using fluorescence labeling and confocal laser scanning microscopy (CLSM). Transforming growth factor-β1 (TGF-β1) was applied to test responsiveness to environmental stimuli.</p><p><strong>Results: </strong>Fibroblast-rich gels contracted uniaxially along the Z-axis but remained laterally stable within the disc, enabling long-term co-culture. Cancer cells showed distinct invasion profiles, with MDA-MB-231 invading significantly deeper than MCF-10 A or MCF-7. Invading cells frequently localized near <i>αSMA</i>-high myofibroblast-like fibroblasts. TGF-β treatment increased fibroblast contractility and further enhanced cancer cell invasion, demonstrating that the system quantitatively detects stromal activation and invasion-promoting cues.</p><p><strong>Conclusion: </strong>The disc-based 3D co-culture system offers a simple and physiologically relevant platform for quantifying cancer cell invasion and fibroblast activation. By supporting fibroblast-rich stromal environments, resolving Z-axis invasion, and responding to external stimuli such as TGF-β, this system provides a practical tool for studying tumor-stroma interactions and may be applicable to patient-derived cells in future studies.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s44164-026-00106-0.</p>","PeriodicalId":73357,"journal":{"name":"In vitro models","volume":"5 1","pages":"79-90"},"PeriodicalIF":2.4,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367430","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}

{"title":"Airways-on-chip models to advance pathology treatment of respiratory organs.","authors":"Elena Fasil, Damiano Rossi, Claudio Ricci, Mario Milazzo, Maurizia Seggiani, Mauro Pistello, Serena Danti","doi":"10.1007/s44164-026-00104-2","DOIUrl":"https://doi.org/10.1007/s44164-026-00104-2","url":null,"abstract":"<p><p>By miniaturizing functional tissue units and recreating physiological-like microenvironments with dynamic stimuli, organ-on-chip (OOC) technology has emerged as a powerful platform for in vitro disease modeling and therapeutic screening. These microfluidic systems are increasingly applied to address major global health challenges, including cancer, owing to their ability to replicate complex tumor microenvironments and metastatic processes. By offering controlled, reproducible conditions for preclinical evaluation, OOCs are accelerating drug discovery and assessment thus they hold great promise for advancing personalized and precision medicine across diverse organ systems, including the airways. This review summarizes recent progress in OOC models for lower and upper airway diseases, spanning lung, trachea and nose, with a key focus on respiratory tract tumors. Here we highlight innovative strategies for recreating pathological airway tissue microenvironments, enabling reliable investigation of respiratory conditions, real-time monitoring of inflammatory responses, as well as evaluation of drug efficacy. Furthermore, we examine how platform design and cell type selection influence the specificity and fidelity of disease modeling, underscoring their critical roles in the development of accurate in vitro systems for studying respiratory diseases and cancer.</p>","PeriodicalId":73357,"journal":{"name":"In vitro models","volume":"5 1","pages":"25-48"},"PeriodicalIF":2.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367474","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}

{"title":"In vitro toxicity evaluation of food-grade silica nanoparticles (E551) in human digestive tract cells.","authors":"Beatriz Roquett, Diego Wiechers, Ana Júlia Fagundes, Ekeveliny A Veschi, Gutemberg Alves, Neilane Rocha, Celso Sant'Anna, José Mauro Granjeiro, Leonardo Boldrini, Wanderson de Souza","doi":"10.1007/s44164-025-00101-x","DOIUrl":"https://doi.org/10.1007/s44164-025-00101-x","url":null,"abstract":"<p><p>Synthetic amorphous silica (SAS, E551) is one of the most widely used food additives, yet uncertainties remain regarding the potential biological effects of its nanoscale fraction. In this study, we performed a metrologically aligned in vitro assessment of food-grade SAS nanoparticles (NPs) in human digestive tract cell models. Detailed physicochemical characterization confirmed their amorphous structure and high purity (EDS, XRD), while dispersion protocols generated two size distributions: ultrasonication (Dispersion A, ~ 238-299 nm) and stirring (Dispersion B, ~ 1300-1600 nm). Dynamic light scattering (DLS) revealed colloidal instability in culture media, with zeta potential decreasing from - 26 mV (water) to ~-9 mV (DMEM). Human colorectal epithelial cells (Caco-2) and gingival fibroblasts (HGF) were exposed to 19.8-200 µg/mL SAS for 72 h. Cell viability remained above 75% in MTT assays, and real-time impedance (xCELLigence) confirmed stable proliferation curves comparable to controls. No increase in intracellular reactive oxygen species was observed, although transmission electron microscopy revealed endocytic uptake with particles confined to cytoplasmic vesicles. Cytokine analysis showed only discrete, dose-dependent modulations, with an increase in MCP-1 (HGF) and VEGF (Caco-2) only at the lower concentration. Scanning electron microscopy (SEM) demonstrated concentration-dependent ultrastructural changes, ranging from elongation of microvilli at 19.8 µg/mL to disorganization of the apical surface at 200 µg/mL. These findings indicate that food-grade SAS does not induce acute cytotoxicity under the tested conditions but can trigger sub-cytotoxic and adaptative morphological and secretory alterations in gastrointestinal cells. Our results emphasize the critical role of dispersion protocols in nanotoxicology and support evidence-based regulation of E551, highlighting the need for chronic and immunological studies to refine its safety profile.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s44164-025-00101-x.</p>","PeriodicalId":73357,"journal":{"name":"In vitro models","volume":"4 3-4","pages":"209-230"},"PeriodicalIF":2.4,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12909697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222116","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}

{"title":"Pre-clinical evaluation of mRNA-lipid nanoparticles' potency and toxicity: current practices and future directions.","authors":"Chloé Muzard, Johanne Seguin, Jonathan Bonnefoy, Nahla Salkini, Vincent Serra, Khair Alhareth, Katia Lemdani, Nathalie Mignet","doi":"10.1007/s44164-025-00096-5","DOIUrl":"https://doi.org/10.1007/s44164-025-00096-5","url":null,"abstract":"<p><p>Over the last few years, the success of COVID-19 mRNA vaccines has resulted in the emergence of RNA lipid nanoparticles (LNPs) with promising prospects for the prevention and treatment of various diseases. The context of the SARS-CoV-2 pandemic has led to the rapid development of vaccines with abbreviated non-clinical programs. However, there are currently no official guidelines defining the required standards for global marketing of mRNA based therapeutic products. Nevertheless, to guarantee a well-controlled product, it is essential to characterize both the drug substance and the final product in terms of their structure, composition, formulation, physico-chemical features, potency, and safety. This lack of guidance has resulted in a wide variety of heterogeneous in vitro tests being used to assess the potency and cytotoxicity of RNA-LNP. This review discusses the commonly used in vitro assays, primarily 2D monolayer assays, employed to evaluate the biological properties of RNA-LNP. We then explore novel alternative methods to bridge the gap between in vitro and in vivo results. We summarize (i) co-culture models, (ii) multilayer 3D assays and (iii) in vivo replacement models, exploring their potential applications in assessing the potency and safety of RNA-LNPs. Finally, we discuss the use of in silico and machine learning as models for optimizing and predicting the biological behavior of RNA-LNPs.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":73357,"journal":{"name":"In vitro models","volume":"4 3-4","pages":"177-194"},"PeriodicalIF":2.4,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12909681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222153","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}

{"title":"Optimization of OSCC spheroid generation for high-throughput drug screening.","authors":"Mansi Dobariya, Seena Sunil, Sai Swetha Uppalapati, Ravindra Taware, Vinal Upadhyay, Amit Mandoli","doi":"10.1007/s44164-025-00099-2","DOIUrl":"https://doi.org/10.1007/s44164-025-00099-2","url":null,"abstract":"<p><strong>Background: </strong>Three-dimensional (3D) spheroid models better replicate the in vivo tumor microenvironment than conventional two-dimensional (2D) cultures, making them valuable tools for preclinical drug screening in oral squamous cell carcinoma (OSCC).</p><p><strong>Methods: </strong>Scaffold-free spheroids were generated from CAL 27 and OECM-1 OSCC cell lines using three approaches: methylcellulose suspension, agarose-coated plates, and ultra-low attachment (ULA) plates. Spheroid morphology and size uniformity were assessed microscopically. Functional characterization included viability assays and histological evaluation for necrosis. Molecular profiling of cancer hallmark genes was performed using qRT-PCR. Drug response assays for cisplatin and doxorubicin were compared between 2D and 3D cultures.</p><p><strong>Results: </strong>Compact, uniform spheroids (~ 150-200 μm) formed within 72 h in both cell lines, with ULA plates producing the highest reproducibility and structural integrity. Histological analysis revealed central necrosis with viable peripheral cell layers. Gene expression analysis confirmed the modulation of hallmark cancer-associated genes in spheroid associated with hypoxia, angiogenesis, stress-response, adhesion and EMT-related pathways. Drug assays demonstrated significantly higher resistance to cisplatin and doxorubicin in 3D spheroids than in 2D monolayers (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>ULA-based 3D spheroids provide a reproducible, structurally stable, and scalable model that closely mimics OSCC tumor biology and chemoresistance. These findings support their application as a robust platform for high-throughput drug screening and translational cancer research.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s44164-025-00099-2.</p>","PeriodicalId":73357,"journal":{"name":"In vitro models","volume":"4 3-4","pages":"195-208"},"PeriodicalIF":2.4,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12909684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222125","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}

{"title":"High-yield isolation of primary human hepatocytes from small liver samples.","authors":"Thea Guy, Jia-Ling Ruan, Carl Lee, Kaitlyn Purdie, David Johnson, Alex Gordon-Weeks, Jagdeep Nanchahal","doi":"10.1007/s44164-025-00097-4","DOIUrl":"https://doi.org/10.1007/s44164-025-00097-4","url":null,"abstract":"<p><strong>Purpose: </strong>Isolation of primary human hepatocytes (PHH) from liver specimens typically relies on the two-step perfusion method, which requires large samples, substantial resources, specialised expertise and suitable vessels for cannulation. Although non-perfusion methods exist, they yield low numbers of hepatocytes and inadequately assess hepatocyte purity. We compared and optimised these methods to develop an improved technique that isolates high yields of viable PHH from non-perfusable liver specimens.</p><p><strong>Method: </strong>In the optimised protocol, non-cancerous resected liver tissue (mean weight: 8.5 ± 2.0 g, SEM) was sliced into 350 μm sections using a vibratome and subjected to a two-step isolation digestion with ethylenediaminetetraacetic acid (EDTA) and collagenase. Cell yield and viability were assessed using propidium iodide staining. Cell populations were characterised by immunofluorescent imaging.</p><p><strong>Results: </strong>The optimised protocol yielded 1.17 ± 0.2 × 10⁶ viable PHH per gram of tissue, approximately 2-fold higher than other non-perfusion protocols, although lower than yields reported for perfusion protocols in the literature. Notably, our protocol achieved an average hepatocyte viability of 80 ± 4%, which surpassed the reported average for published non-perfusion methods. Staining for glycogen and albumin secretion confirmed the functional integrity of the isolated PHH. The protocol was also effective with steatotic liver tissue, yielding 1.0 ± 0.1 × 10⁶ viable PHH per gram with 83 ± 2% viability. Most liver specimens were obtained from patients who had undergone neoadjuvant chemotherapy, however, no trend related to chemotherapy treatment was observed.</p><p><strong>Conclusions: </strong>Our non-perfusion protocol permits the isolation of viable and functional PHH from a diverse range of liver samples. This advancement provides a practical alternative to perfusion methods and will extend the use of PHH in research and drug development.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s44164-025-00097-4.</p>","PeriodicalId":73357,"journal":{"name":"In vitro models","volume":"4 3-4","pages":"245-259"},"PeriodicalIF":2.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12909712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222119","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}

{"title":"Gellan Gum-based Bioink for Bioprinting of a Mechanically Mimetic 3D in vitro Liver Model.","authors":"Natália Akemi Kohori, Ibrahim Fatih Cengiz, Mariana Carvalho, Joana Silva-Correia, Ricardo A Pires, Carla Dos Santos Riccardi, Lilian Cristina Pereira, Rui L Reis, Joaquim Miguel Oliveira","doi":"10.1007/s44164-025-00094-7","DOIUrl":"https://doi.org/10.1007/s44164-025-00094-7","url":null,"abstract":"<p><p>The liver is vital for the human body's metabolism, making the development of more predictable and reproducible pathophysiological-relevant three-dimensional (3D) liver models crucial for studying the accumulation of xenobiotics and associated liver diseases. In this work, we describe the development of a bioink comprising 0.2% w/v TayaGel® HA (high acyl gellan gum) and 1.2% w/v Gelzan™ CM (low acyl gellan gum) for the bioprinting of 3D liver models. The bioink underwent physicochemical characterization, including rheological and dynamic mechanical analyses, and cytotoxicity testing using HepG2 cell line in vitro. The shape fidelity assay suggested an ink fluid-like behavior and good filament formation with Young's modulus resembling liver tissue. Moreover, the dynamic mechanical analysis showed the tan δ aligned with liver tissue, while the hydrogel degraded over 60% within 24 h. No increase in cell number and low viability were observed in loaded cells during 7 days of cultivation. Furthermore, the hydrogel presented a non-angiogenic nature on the chicken chorioallantoic membrane model. Collectively, these findings highlight the potential of gellan gum (GG), particularly high acyl gellan gum, as a bioink due to its mechanical mimicry and suitability for bioprinted 3D in vitro as sacrificial bioink, combining soft-elastic properties with controlled degradation.</p>","PeriodicalId":73357,"journal":{"name":"In vitro models","volume":"4 3-4","pages":"231-244"},"PeriodicalIF":2.4,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12909728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222097","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}

{"title":"Development of a functional sarcopenia model utilizing a microcantilever microphysiological system as a phenotypic disease model.","authors":"Himanshi Jangir, Leandro H Gallo, Russell Emmons, James J Hickman","doi":"10.1007/s44164-025-00092-9","DOIUrl":"https://doi.org/10.1007/s44164-025-00092-9","url":null,"abstract":"<p><strong>Purpose: </strong>Sarcopenia is a skeletal muscle (SKM) condition marked by reduced muscle mass and function and is often observed as a comorbidity with inflammatory conditions.</p><p><strong>Methods: </strong>We have developed a defined in vitro functional model to study sarcopenia by incubating human-induced pluripotent stem cell-derived SKM cells with 3 nM TNF-alpha (TNFα) for 96 h. The long-term effects of this treatment were studied for up to 32 days in culture. Muscle function was evaluated by measuring myotube width as well as microcantilever contraction amplitude, force, and fatigue index.</p><p><strong>Results: </strong>This model revealed the maintenance of a significant reduction in myotube width for 32 days after TNF-α treatment; moreover, a decrease in myotube contraction amplitude and an increase in fatigue indices were recorded for 32 days. In addition, disease progression and tissue degradation of the sarcopenic conditions were monitored for higher reactive oxygen species production for both acute (day 4) and chronic (day 40) timelines.</p><p><strong>Conclusion: </strong>This is the first microphysiological system for sarcopenia evaluation that can be used to evaluate therapeutics. This device can now be combined in a multi-organ microphysiological system to study sarcopenia induced by an inflammatory response from other organs or as a comorbidity in the platform.</p><p><strong>Graphical abstract: </strong>Development of the first defined in vitro functional model of sarcopenia on a microcantilever platform. This study recapitulates physiological signatures of disease progression characterized by loss of muscle mass and function and an increase in reactive oxygen species.</p>","PeriodicalId":73357,"journal":{"name":"In vitro models","volume":"5 1","pages":"63-78"},"PeriodicalIF":2.4,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367410","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}

{"title":"ECM-free lung tumoroids generated by an air-stretchable microfluidic chip.","authors":"Talha Chauhdari, Jilei Su, Jiabao Lv, Yongsheng Ding","doi":"10.1007/s44164-025-00093-8","DOIUrl":"https://doi.org/10.1007/s44164-025-00093-8","url":null,"abstract":"<p><p>Lung cancer remains the leading cause of cancer-related mortality worldwide, highlighting an urgent need for improved therapeutic strategies and more physiologically relevant in vitro models to better understand lung tumor biology and accelerate drug screening. Traditional in vivo tumor-bearing grafting model, despite their biological complexity, present significant limitations due to interspecies differences that hinder accurate recapitulation of the human tumor microenvironment (TME) and drug responses. On the other hand, existing in vitro models often fail to fully replicate the dynamic biochemical and biomechanical cues that are present in vivo. However, more recently, three-dimensional (3D) in vitro models, including organoids, tumoroids, and spheroids, have emerged as promising models that mimic TME. The conventional tumoroid generation relies on costly commercial extracellular matrix (ECM). Here, we introduced a microfluidic chip-based lung tumoroid model capable of mimicking alveolar stretching and air-liquid interface (ALI). Our model integrates three types of cells: lung cancer, endothelial, and fibroblast cells, enabling their self-aggregation into tumoroids without extragenous ECM. We also compared tumoroid formation capacity among three lung cancer cell lines, revealing that NCI-H1299, highly metastatic cells, failed to form tumoroids due to low E-cadherin expression. Furthermore, the drug testing demonstrated that the tumoroids exposed to ALI and cyclic stretch exhibited increased drug resistance compared to the static control, emphasizing the importance of mechanical cues in modulating tumor behaviors. This new in vitro model offers a more physiologically relevant platform to study lung cancer biology and drug screening, potentially accelerating the development of effective lung cancer therapies.</p>","PeriodicalId":73357,"journal":{"name":"In vitro models","volume":"5 1","pages":"49-61"},"PeriodicalIF":2.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367459","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}

{"title":"The role of ABC transporters in the human lung epithelium-insights from and limitations of current in vitro cell models.","authors":"Sina Simon, Carina Cantrill, Claus-Michael Lehr","doi":"10.1007/s44164-025-00091-w","DOIUrl":"https://doi.org/10.1007/s44164-025-00091-w","url":null,"abstract":"<p><p>ATP-binding cassette (ABC) drug transporter proteins are expressed at the level of the human pulmonary epithelium. This protein superfamily is known to clinically affect the pharmacokinetics of their substrates in tissues such as the intestine or liver. In contrast, it is not yet entirely understood to what degree ABC transporters contribute as drivers of pulmonary distribution. In recent decades, a number of in vitro studies have been conducted to elucidate the role of ABC transporter in the human lung including human derived cell lines, primary cells and human lung tissue. Results indicate the functional expression of ABC transporters in vitro. However, ABC expression patterns vary across the different cells mimicking upper and lower airways. Since the lung is a target for a variety of drug classes, it is of importance to understand the influence of ABC transporters to pulmonary drug disposition and local drug exposure levels. This review gives an overview over conducted in vitro studies that do not focus only on ABC transporters' expression but also on assessing their functional activity. Moreover, we pinpoint important aspects that need to be taken into account when conducting these in vitro bidirectional transporter efflux studies. This contributes to a better understanding of the importance of these pulmonary in vitro studies and provides guidance on how to interpret and conduct these studies.</p>","PeriodicalId":73357,"journal":{"name":"In vitro models","volume":"5 1","pages":"1-23"},"PeriodicalIF":2.4,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12957684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147367426","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}