3D cell culture models in research: applications to lung cancer pharmacology DOI Creative Commons
Nathan Vella, Anthony G. Fenech,

Vanessa Petroni Magri

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 23, 2024

Lung cancer remains one of the leading causes cancer-related mortality worldwide, necessitating innovative research methodologies to improve treatment outcomes and develop novel strategies. The advent three-dimensional (3D) cell cultures has marked a significant advancement in lung research, offering more physiologically relevant model compared traditional two-dimensional (2D) cultures. This review elucidates various types 3D culture models currently used pharmacology, including spheroids, organoids engineered tissue models, having pivotal roles enhancing our understanding biology, facilitating drug development, advancing precision medicine. systems mimic complex spatial architecture microenvironment tumours, providing critical insights into cellular molecular mechanisms tumour progression, metastasis responses. Spheroids, derived from commercialized lines, effectively (TME), formation hypoxic nutrient gradients, crucial for evaluating penetration efficacy anti-cancer therapeutics. Organoids tumouroids, primary tissues, recapitulate heterogeneity cancers are instrumental personalized medicine approaches, supporting simulation vivo pharmacological responses patient-specific context. Moreover, these have been co-cultured with biomimicry extracellular matrix (ECM) components further heterotypic cell-cell cell-ECM interactions present within TME. significantly contributing identification therapeutic targets resistance against conventional therapies. Therefore, this summarizes latest findings involving together common laboratory-based assays study effects. Additionally, integration development workflows is discussed. accelerating translation laboratory clinical applications, thereby landscape treatment. By closely mirroring human not only enhance disease but also pave way effective

Language: Английский

Microfluidic Droplet-Assisted Fabrication of Vessel-Supported Tumors for Preclinical Drug Discovery DOI Creative Commons
Yue Wu, Yuwen Zhao, Yuyuan Zhou

et al.

ACS Applied Materials & Interfaces, Journal Year: 2023, Volume and Issue: 15(12), P. 15152 - 15161

Published: March 15, 2023

High-fidelity

Language: Английский

Citations

15
Recent advances in vascularized tumor-on-a-chip DOI Creative Commons

Christina Bao Xian Huang,

Ting‐Yuan Tu

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: March 30, 2023

The vasculature plays a critical role in cancer progression and metastasis, representing pivotal aspect the creation of models. In recent years, emergence organ-on-a-chip technology has proven to be robust tool, capable replicating vivo conditions with exceptional spatiotemporal resolution, making it significant asset research. This review delves into latest developments 3D microfluidic vascularized tumor models their applications vitro , focusing on heterotypic cellular interactions, mechanisms therapeutic screening. Additionally, examines benefits drawbacks these models, as well future prospects for advancement.

Language: Английский

Citations

15
Bridging the gap between tumor-on-chip and clinics: a systematic review of 15 years of studies DOI Creative Commons
Charlotte Bouquerel,

Anastasiia Dubrova,

Isabella Hofer

et al.

Lab on a Chip, Journal Year: 2023, Volume and Issue: 23(18), P. 3906 - 3935

Published: Jan. 1, 2023

Over the past 15 years, field of oncology research has witnessed significant progress in development new cell culture models, such as tumor-on-chip (ToC) systems. In this comprehensive overview, we present a multidisciplinary perspective by bringing together physicists, biologists, clinicians, and experts from pharmaceutical companies to highlight current state ToC research, its unique features, challenges it faces. To offer readers clear quantitative understanding field, conducted an extensive systematic analysis more than 300 publications related 2005 2022. key advantages over other vitro models enabling precise control various parameters. These parameters include properties extracellular matrix, mechanical forces exerted on cells, physico-chemical environment, composition, architecture tumor microenvironment. Such fine allows closely replicate complex microenvironment interactions within tumors, facilitating study cancer progression therapeutic responses highly representative manner. Importantly, incorporating patient-derived cells or xenografts, have demonstrated promising results terms clinical validation. We also examined potential for industries which adoption is expected occur gradually. Looking ahead, given high failure rate trials increasing emphasis 3Rs principles (replacement, reduction, refinement animal experimentation), hold immense research. next decade, data generated could potentially be employed discovering targets, contributing regulatory purposes, refining preclinical drug testing reducing reliance models.

Language: Английский

Citations

15
Microphysiological systems as models for immunologically ‘cold’ tumors DOI Creative Commons

Daniela Gaebler,

Stephanie J. Hachey, Christopher C.W. Hughes

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: April 22, 2024

The tumor microenvironment (TME) is a diverse milieu of cells including cancerous and non-cancerous such as fibroblasts, pericytes, endothelial immune cells. intricate cellular interactions within the TME hold central role in shaping dynamics cancer progression, influencing pivotal aspects initiation, growth, invasion, response to therapeutic interventions, emergence drug resistance. In immunologically 'cold' tumors, marked by scarcity infiltrating cells, limited antigen presentation absence potent immune-stimulating signals, an abundance immunosuppressive factors. While strategies targeting avenue tumors have emerged, there pressing need for novel approaches that faithfully replicate complex non-cellular order develop targeted therapies can effectively stimulate responses improve outcomes patients. Microfluidic devices offer distinct advantages over traditional vitro 3D co-culture models vivo animal models, they better recapitulate key characteristics allow precise, controlled insights into dynamic interplay between various immune, stromal cell types at any timepoint. This review aims underscore microfluidic systems advancing our understanding presents current model aim dissect tumor-stromal, tumor-immune immune-stromal tumors. Understanding intricacies crucial devising effective reinvigorate overcome challenges immunotherapy approaches.

Language: Английский

Citations

4
Microphysiologically Engineered Vessel-Tumor Model to Investigate Vascular Transport Dynamics of Immune Cells DOI Creative Commons
Yuwen Zhao, Yue Wu, Khayrul Islam

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: unknown

Published: April 23, 2024

Cancer immunotherapy has emerged as a promising therapeutic strategy to combat cancer effectively. However, it is hard observe and quantify how this in vivo process happens. Three-dimensional (3D) microfluidic vessel-tumor models offer valuable capability study immune cells transport during progression. We presented an advanced 3D vessel-supported tumor model consisting of the endothelial lumen vessel network for T cells' transportation. The cell through interaction with spheroids was represented monitored vitro. Specifically, we demonstrate that glycocalyx serving can influence endothelium-immune interaction. Furthermore, after vascular transport, programmed death protein 1 (PD-1) checkpoint inhibition influences delivered activated-T on killing evaluated. Our vitro provides microphysiologically engineered platform represent transportation immunotherapy. reported innovative believed have potential explore tumor-induced response mechanism preclinically evaluate immunotherapy's effectiveness.

Language: Английский

Citations

4
Mimicking blood and lymphatic vasculatures using microfluidic systems DOI Creative Commons
Eva Hall, Kailee Mendiola, N. Keilany Lightsey

et al.

Biomicrofluidics, Journal Year: 2024, Volume and Issue: 18(3)

Published: May 1, 2024

The role of the circulatory system, containing blood and lymphatic vasculatures, within body, has become increasingly focused on by researchers as dysfunction either systems been linked to serious complications disease. Currently,

Language: Английский

Citations

4
Human 3D Ovarian Cancer Models Reveal Malignant Cell–Intrinsic and –Extrinsic Factors That Influence CAR T-cell Activity DOI Creative Commons
Joash D. Joy, Beatrice Malacrida, Florian Laforêts

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(15), P. 2432 - 2449

Published: May 31, 2024

Abstract In vitro preclinical testing of chimeric antigen receptor (CAR) T cells is mostly carried out in monolayer cell cultures. However, alternative strategies are needed to take into account the complexity and effects tumor microenvironment. Here, we describe modulation CAR T-cell activity by malignant fibroblasts human three-dimensional (3D) models increasing complexity. combining mucin-1 (MUC1) TnMUC1 with high-grade serous ovarian cancer spheroids, cell–intrinsic resistance killing was due defective death signaling involving TNFα. Adding primary spheroids unexpectedly increased ability kill resistant as CCL2 produced activated CCR2/4+ cells. culturing collagen gels engendered production a dense extracellular matrix that impeded TGFβ-dependent manner. A vascularized microfluidic device developed allowed flow through vessels penetrate more physiological way, TNFα-dependent Complex 3D may provide an efficient way screening multiple cytotoxic immune constructs while also enabling evaluation mechanisms cell–cell cell–matrix interactions, thus accelerating research on therapies solid tumors. Significance: Three-dimensional uncover tumors, which could help accelerate development improved constructs.

Language: Английский

Citations

4
Demonstration of Enhancement of Tumor Intravasation by Dicarbonyl Stress Using a Microfluidic Organ‐on‐chip DOI
Nilesh Kumar,

Bidita Samanta,

Jyothsna KM

et al.

Small, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Abstract Cancer metastasis involves cell migration from their primary organ foci into vascular channels, followed by dissemination to prospective colonization sites. Vascular entry of tumor cells or intravasation breaching stromal and endothelial extracellular matrix (ECM) the barriers. How kinetics this breach are confounded chronic inflammatory stresses seen in diabetes aging remains ill‐investigated. To study problem, a histopathology‐motivated, imaging‐tractable, microfluidic multi‐organ‐on‐chip platform is constructed, that seamlessly integrates breast tumor‐like compartment: invasive MDA‐MB‐231 3D Collagen I scaffold, flow‐implemented channel: immortalized human aortic endothelia (TeloHAEC) on laminin‐rich basement membrane (lrBM). The chip showcases complexity intravasation, wherein cooperate form anastomotic structures, which facilitate cancer channel. Upon entry, adhere flow within Exposure methylglyoxal (MG), dicarbonyl stressor associated with diabetic circulatory milieu increases adhesion through This can be driven MG‐induced senescence shedding, but also ability MG degrade lrBM pathologically cross‐link I, diminishing cell‐ECM adhesion. Thus, stress attenuates homeostatic barriers exacerbating metastasis.

Language: Английский

Citations

0
In vitro integration of a functional vasculature to model endothelial regulation of chemotherapy and T-cell immunotherapy in liver cancer DOI Creative Commons
Jyothsna Vasudevan,

Ragavi Vijayakumar,

Jose Antonio Reales‐Calderón

et al.

Biomaterials, Journal Year: 2025, Volume and Issue: 320, P. 123175 - 123175

Published: Feb. 9, 2025

Language: Английский

Citations

0
Emerging Hydrophobized Surfaces for Rapid Fabrication of 3D Tumor Models DOI
Maria V. Monteiro, Mariana T. Carvalho, Beatriz S. Moura

et al.

ACS Materials Letters, Journal Year: 2025, Volume and Issue: unknown, P. 961 - 973

Published: Feb. 11, 2025

Language: Английский

Citations

0