Lab-on-chip technologies for exploring the gut–immune axis in metabolic disease

Lab on a Chip, Год журнала: 2024, Номер 24(5), С. 1266 - 1292

Опубликована: Янв. 1, 2024

Further development of lab-on-chip platforms is required to create an environment capable hosting more complex microbiota and immune cells.

Язык: Английский

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In vitro immunity: an overview of immunocompetent organ-on-chip models

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Май 21, 2024

Impressive advances have been made to replicate human physiology in vitro over the last few years due growth of organ-on-chip (OoC) field both industrial and academic settings. OoCs are a type microphysiological system (MPS) that imitates functional dynamic aspects native organ biology on microfluidic device. Organoids organotypic models, ranging their complexity from simple single-cell complex multi-cell constructs, being incorporated into OoC devices better mimic physiology. technology has now progressed stage at which it received official recognition by Food Drug Administration (FDA) for use as an alternative standard procedures drug development, such animal studies traditional assays. However, area is still lagging behind incorporation immune system, critical element required investigate health disease. In this review, we summarise progress integrate immunology various systems, specifically focusing models related barriers lymphoid organs. These utilise either commercially available or custom-made. This review explores difference between innate adaptive cells role modelling organ-specific diseases OoCs. Immunocompetent multi-OoC also highlighted extent they recapitulate systemic discussed. Together, aim describe current state immune-OoCs, limitations future perspectives needed improve field.

Язык: Английский

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A Novel Multicompartment Barrier‐Free Microfluidic Device Reveals the Impact of Extracellular Matrix Stiffening and Temozolomide on Immune‐Tumor Interactions in Glioblastoma

Small, Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

Abstract The immune system plays a crucial role in shaping the glioblastoma tumor microenvironment, characterized by its complexity and dynamic interactions. Understanding tumor‐immune crosstalk is essential for advancing cancer research therapeutic development. Here, novel multicompartment, barrier‐free microfluidic device presented that overcomes limitations of existing models enabling direct interactions without physical barriers, preserving natural cell infiltration. This platform supports independent simultaneous culture cells, replicating healthy‐tumoral stroma interface, allows investigating effect matrix stiffness chemotherapy on both populations. findings reveal increased collagen concentration promotes invasiveness while impairing Additionally, temozolomide treatment reduces motility but enhances anti‐tumor responses. These insights highlight critical roles extracellular mechanics progression modulation, establishing this as powerful tool studying glioblastoma‐immune dynamics evaluating strategies.

Язык: Английский

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Lymph Node-on-Chip Technology: Cutting-Edge Advances in Immune Microenvironment Simulation

Pharmaceutics, Год журнала: 2024, Номер 16(5), С. 666 - 666

Опубликована: Май 16, 2024

Organ-on-a-chip technology is attracting growing interest across various domains as a crucial platform for drug screening and testing set to play significant role in precision medicine research. Lymph nodes, being intricately structured organs essential the body’s adaptive immune responses antigens foreign particles, are pivotal assessing immunotoxicity of novel pharmaceuticals. Significant progress has been made research on structure function lymphatic system. However, there still an urgent need develop prospective tools techniques delve deeper into its diseases’ pathological physiological processes corresponding immunotherapeutic therapies. Organ chips can accurately reproduce specific functional areas lymph nodes better simulate complex microstructure interactions between different cells, which convenient studying biological processes. This paper reviews existing node their design approaches. It discusses applications above systems modeling cell motility, cell–cell interactions, vaccine responses, testing, cancer Finally, we summarize challenges that current faces terms structure, source, extracellular matrix simulation provide outlook future direction integrated system chips.

Язык: Английский

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Modeling reproductive and pregnancy-associated tissues using organ-on-chip platforms: challenges, limitations, and the high throughput data frontier

Frontiers in Bioengineering and Biotechnology, Год журнала: 2025, Номер 13

Опубликована: Апрель 1, 2025

Over the past decade, organ-on-chip technology (microphysiological systems or tissue chips) has reshaped in-vitro physiological and pathological modeling pharmaceutical drug assessment. FDA Modernization Act 2.0 allows for alternatives to animal testing use of appropriate non-animal models/new approach methods (NAMs), such as Organ-on-chips (OC) platforms in silico simulation models, generate pre-clinical trial data regulatory purposes primes microfluidic field have exponential growth coming years. The changes approaches agencies could significantly impact development therapeutics during pregnancy. However, limitations devices molecular biochemical assay shortfalls hinder progress OOC field. This review describes available reproductive pregnancy-related platforms, current methodologies utilized endpoint datasets (e.g., microscopic imaging, immunocytochemistry, real-time polymerase chain reaction, cytokine multiplex analysis). Microfluidic platform limitations, fewer number cells low supernatant volumes restrictions regarding fabrication materials, are described. Novel spatial transcriptomics, imaging cytometry by time flight, exosomes analysis using Exoview) overcome these challenges primed provide biologically relevant clinically translational that can revolutionize modeling, discovery, toxicologic risk engineering adaptations increase throughput (i.e., device arrays) biological advancements improve both needed reach their full potential.

Язык: Английский

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Development of Drug Efficacy Testing Platform for Glomerulonephritis

Micromachines, Год журнала: 2024, Номер 15(3), С. 317 - 317

Опубликована: Фев. 24, 2024

We developed a 3D glomeruli tissue chip for glomerulonephritis (GN) testing, featuring gravity-driven glomerular filtration barrier (GFB) with human podocytes and endothelial cells bidirectional flow in the bottom channel. Using puromycin-induced GN, we observed decreased cell viability, increased albumin permeability, reduced WT1 nephrin compared to normal GFB. Tacrolimus restored expression. serum from five membranous nephropathy (MN) patients, created MN models using GFB-mimicking chip. A notable decline viability was serum-induced MN1 MN2 models. However, tacrolimus it. Albumin permeability MN1, MN2, MN5 by treatment. displayed best clinical response tacrolimus, exhibiting expression of chip-based evaluations after successfully evaluated efficacy GN on that mimicked structure function The holds promise as personalized platform assessing drug patient samples.

Язык: Английский

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Human In Vitro Models of Neuroenergetics and Neurometabolic Disturbances: Current Advances and Clinical Perspectives

Stem Cells Translational Medicine, Год журнала: 2024, Номер 13(6), С. 505 - 514

Опубликована: Апрель 8, 2024

Neurological conditions conquer the world; they are leading cause of disability and second death worldwide, appear all around world in every age group, gender, nationality, socioeconomic class. Despite growing evidence an immense impact perturbations neuroenergetics on overall brain function, only little is known about underlying mechanisms. Especially human insights sparse, owing to a shortage physiologically relevant model systems. With this perspective, we aim explore key steps considerations involved developing advanced vitro for studying neuroenergetics. We discuss biological technological strategies meet requirements predictive model, aiming at providing guide inspiration future models

Язык: Английский

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Immune response to IL6 gradient in a diffusion-based microfluidic labchip

Sensors and Actuators B Chemical, Год журнала: 2024, Номер 417, С. 136141 - 136141

Опубликована: Июнь 13, 2024

Язык: Английский

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A compartmentalized microfluidic platform to investigate immune cells cross-talk in rheumatoid arthritis

Biofabrication, Год журнала: 2024, Номер 17(1), С. 015008 - 015008

Опубликована: Сен. 27, 2024

The dysregulation of the immune system plays a crucial role in pathogenesis manyfold diseases, among which we find rheumatoid arthritis (RA), an autoimmune disease characterized by chronic inflammation synovial joints, leading to pain and disability. Immune cells such as pro-inflammatory macrophages T helper 1 (Th1) drive inflammatory cascade. Thus, including inin vitromodels is pivotal recapitulate better understand complex interactions between these cell subsets their secreted mediators. Here, compartmentalized microfluidic platform presented, for precise confinement circulating organs-on-chip. integration innovative normally-closed sieving valves allows, through minimal waste biological material, co-culture different types (e.g. Th1). Moreover, allows stimulate separately, assess cross-talk at desired time points. Functional validation demonstrates its ability create stable chemotactic gradients, allowing induction evaluation Th1 migration. In proof-of-concept study, allowed migration towards macrophages, thus replicating characteristic interaction triggered during RA onset. These results support suitability study phenomena, being potentially applicable mechanisms, both involved progression immune-mediated pathologies.

Язык: Английский

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Leveraging Organ‐on‐Chip Models to Investigate Host–Microbiota Dynamics and Targeted Therapies for Inflammatory Bowel Disease

Advanced Healthcare Materials, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 3, 2024

Abstract Inflammatory bowel disease (IBD) is an idiopathic gastrointestinal with drastically increasing incidence rates. Due to its multifactorial etiology, a precise investigation of the pathogenesis extremely difficult. Although reductionist cell culture models and more complex in animals have clarified understanding individual mechanisms contributing factors IBD past, it remains challenging bridge research clinical practice. Conventional 2D cannot replicate host–microbiota interactions stable long‐term microbial culture. Further, extrapolating data from animal patients due genetic environmental diversity leading differences immune responses. Human intestine organ‐on‐chip (OoC) emerged as alternative vitro model approach investigate IBD. OoC not only recapitulate human intestinal microenvironment accurately than cultures yet may also be advantageous for identification important disease‐driving pharmacological interventions targets possibility emulating different complexities. The predispositions biological hallmarks focusing on at mucosal barrier are elucidated here. Additionally, potential OoCs explore microbiota‐related therapies personalized medicine treatment discussed.

Язык: Английский

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