Cancer-on-chip: a 3D model for the study of the tumor microenvironment

Journal of Biological Engineering, Год журнала: 2023, Номер 17(1)

Опубликована: Авг. 17, 2023

Abstract The approval of anticancer therapeutic strategies is still slowed down by the lack models able to faithfully reproduce in vivo cancer physiology. On one hand, conventional vitro fail recapitulate organ and tissue structures, fluid flows, mechanical stimuli characterizing human body compartments. other animal cannot typical tumor microenvironment, essential study behavior progression. This reviews cancer-on-chips as most promising tools model investigate microenvironment metastasis. We also described how cancer-on-chip devices have been developed implemented common primary cancers their metastatic sites. Pros cons this technology are then discussed highlighting future challenges close gap between pre-clinical clinical studies accelerate new therapies humans.

Язык: Английский

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Cancer Models on Chip: Paving the Way to Large‐Scale Trial Applications

Advanced Materials, Год журнала: 2023, Номер 35(35)

Опубликована: Апрель 27, 2023

Abstract Cancer kills millions of individuals every year all over the world (Global Observatory). The physiological and biomechanical processes underlying tumor are still poorly understood, hindering researchers from creating new, effective therapies. Inconsistent results preclinical research, in vivo testing, clinical trials decrease drug approval rates. 3D tumor‐on‐a‐chip (ToC) models integrate biomaterials, tissue engineering, fabrication microarchitectures, sensory actuation systems a single device, enabling reliable studies fundamental oncology pharmacology. This review includes critical discussion about their ability to reproduce microenvironment (TME), advantages drawbacks existing architectures, major components techniques. focus is on current materials micro/nanofabrication techniques used manufacture reproducible microfluidic ToC for large‐scale trial applications.

Язык: Английский

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A Self‐Assembled 3D Model Demonstrates How Stiffness Educates Tumor Cell Phenotypes and Therapy Resistance in Pancreatic Cancer

Advanced Healthcare Materials, Год журнала: 2024, Номер 13(17)

Опубликована: Март 12, 2024

Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense and stiff extracellular matrix (ECM) associated with tumor progression therapy resistance. To further the understanding of how stiffening microenvironment (TME) contributes to aggressiveness, three‐dimensional (3D) self‐assembling hydrogel disease model developed based on peptide amphiphiles (PAs, PA‐E3Y ) designed tailor stiffness. The displays nanofibrous architectures reminiscent native TME enables study invasive behavior PDAC cells. Enhanced tuneability stiffness demonstrated interacting thermally annealed aqueous solutions (PA‐E3Y h divalent cations create hydrogels mechanical properties ultrastructure similar ECM. It shown that levels found in induces ECM deposition, promotes epithelial‐to‐mesenchymal transition (EMT), enriches CD133 + /CXCR4 cancer stem cells (CSCs), subsequently enhances drug findings reveal 3D environment renders more aggressive therefore faithfully recapitulates vivo tumors.

Язык: Английский

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Therapeutic Strategies to Overcome Fibrotic Barriers to Nanomedicine in the Pancreatic Tumor Microenvironment

Cancers, Год журнала: 2023, Номер 15(3), С. 724 - 724

Опубликована: Янв. 24, 2023

Pancreatic cancer is notorious for its dismal prognosis. The enhanced permeability and retention (EPR) effect theory posits that nanomedicines (therapeutics in the size range of approximately 10–200 nm) selectively accumulate tumors. Nanomedicine has thus been suggested to be “magic bullet”—both effective safe—to treat pancreatic cancer. However, densely fibrotic tumor microenvironment impedes nanomedicine delivery. EPR insufficient achieve a significant therapeutic effect. Intratumoral fibrosis chiefly driven by aberrantly activated fibroblasts extracellular matrix (ECM) components secreted. Fibroblast ECM abnormalities offer various potential targets intervention. In this review, we detail diverse strategies being tested overcome barriers Strategies target tissue/process are discussed first, which followed optimize design. We provide an overview how deeper understanding, increasingly at single-cell resolution, fibroblast biology revealing complex role stroma pathogenesis consider implications. Finally, discuss critical gaps our understanding might better formulate successfully

Язык: Английский

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Embedded bioprinted multicellular spheroids modeling pancreatic cancer bioarchitecture towards advanced drug therapy

Journal of Materials Chemistry B, Год журнала: 2024, Номер 12(7), С. 1788 - 1797

Опубликована: Янв. 1, 2024

A facile embedded dot bioprinting system for bioengineering desmoplastic PDAC spheroids with scalable, flexible and robust performance, or multi-type spheroid patterns advanced drug therapy disease mechanism exploration, is introduced.

Язык: Английский

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An Insight on Microfluidic Organ-on-a-Chip Models for PM_2.5-Induced Pulmonary Complications

ACS Omega, Год журнала: 2024, Номер 9(12), С. 13534 - 13555

Опубликована: Март 7, 2024

Pulmonary diseases like asthma, chronic obstructive pulmonary disorder, lung fibrosis, and cancer pose a significant burden to global human health. Many of these complications arise as result exposure particulate matter (PM), which has been examined in several preclinical clinical trials for its effect on respiratory diseases. Particulate size less than 2.5 μm (PM2.5) known inflict unforeseen repercussions, although data from epidemiological studies back this are pending. Conventionally utilized two-dimensional (2D) cell culture animal models have provided insufficient benefits emulating the vivo physiological pathological conditions. Three-dimensional (3D) structural models, including organ-on-a-chip experienced developmental upsurge recent times. Lung-on-a-chip potential simulate specific features lungs. With advancement technology, an emerging advanced technique termed microfluidic developed with aim identifying complexity cellular microenvironment body. In present Review, role lung-on-a-chip modeling reproducing explored, emphasis PM2.5-induced complications.

Язык: Английский

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3D Collagen-Nanocellulose Matrices Model the Tumour Microenvironment of Pancreatic Cancer

Frontiers in Digital Health, Год журнала: 2021, Номер 3

Опубликована: Июль 26, 2021

Three-dimensional (3D) cancer models are invaluable tools designed to study tumour biology and new treatments. Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest types cancer, has been progressively explored with bioengineered 3D approaches by deconstructing elements its microenvironment. Here, we investigated suitability collagen-nanocellulose hydrogels mimic extracellular matrix PDAC promote formation spheroids multicellular cultures stromal cells. Blending type I collagen fibrils cellulose nanofibres formed a controllable stiffness, which resembled lower profile pancreatic tissues. Collagen-nanocellulose supported growth cultures, increased metabolic activity stiffness. To validate our model, tested individual combined effects anti-cancer compound triptolide chemotherapeutics gemcitabine paclitaxel, resulting in differential cell responses. Our blended matrices tuneable mechanical properties consistently maintain cells cellular microenvironment allow screening

Язык: Английский

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Programmable Living Units for Emulating Pancreatic Tumor‐Stroma Interplay

Advanced Healthcare Materials, Год журнала: 2022, Номер 11(13)

Опубликована: Апрель 15, 2022

Bioengineering close-to-native in vitro models that emulate tumors bioarchitecture and microenvironment is highly appreciable for improving disease modeling toolboxes. Herein, pancreatic cancer living units-so termed cancer-on-a-bead models-are generated. Such user-programmable platforms exhibit biomimetic multicompartmentalization tunable integration of associated stromal elements. These stratified units can be rapidly assembled in-air, reproducible morphological features, size, recapitulate spatially resolved tumor-stroma extracellular matrix (ECM) niches. Compartmentalization cells well-defined ECM microenvironments stimulates the secretion key biomolecular effectors including transforming growth factor β Interleukin 1-β, closely emulating signatures human tumors. Cancer-on-a-bead also display increased drug resistance to chemotherapeutics when compared their reductionistic counterparts, reinforcing importance differentially model components inclusion spatial stratification as observed vivo. Beyond providing a universal technology enables modularity elements bioengineering, scalable, in-air fabrication ECM-tunable 3D leveraged recapitulating differential composition occurring other neoplasias provided here.

Язык: Английский

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Highly Mimetic Ex Vivo Lung‐Cancer Spheroid‐Based Physiological Model for Clinical Precision Therapeutics

Advanced Science, Год журнала: 2023, Номер 10(16)

Опубликована: Апрель 21, 2023

Abstract Lung cancer remains a major health problem despite the considerable research into prevention and treatment methods. Through deeper understanding of tumors, patient‐specific ex vivo spheroid models with high specificity can be used to accurately investigate cause, metastasis, strategies for lung cancer. Biofabricate tumors are presented, consisting patient‐derived tumor spheroids, endothelial cells, decellularized extracellular matrix, which maintain radial oxygen gradient, as well biophysicochemical behaviors native precision medicine. It is also demonstrated that developed lung‐cancer model reproduces patient responses chemotherapeutics targeted therapy in co‐clinical trial, 85% accuracy, 86.7% sensitivity, 80% specificity. RNA sequencing analysis validates gene expression spheroids replicates patient's primary tumor. This an predictive personalized improve quality clinical care.

Язык: Английский

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LncRNA GAS6-AS1 contributes to 5-fluorouracil resistance in colorectal cancer by facilitating the binding of PCBP1 with MCM3

Cancer Letters, Год журнала: 2024, Номер 589, С. 216828 - 216828

Опубликована: Март 22, 2024

5-Fluorouracil (5-FU) resistance has always been a formidable obstacle in the adjuvant treatment of advanced colorectal cancer (CRC). In recent years, long non-coding RNAs have emerged as key regulators various pathophysiological processes including 5-FU resistance. TRG is postoperative pathological score chemotherapy effectiveness for CRC, which 0–1 classified sensitivity and 3 Here, RNA-seq combined with weighted gene correlation network analysis confirmed close association GAS6-AS1 TRG. expression was positively correlated clinicopathological features poor prognosis CRC. increased 50% inhibiting concentration 5-FU, enhanced cell proliferation accelerated G1/S transition, both without vitro vivo. Mechanistically, stability MCM3 mRNA by recruiting PCBP1, consequently increasing expression. Furthermore, PCBP1 counteracted effects on Notably, PDX model indicated that combining chemotherapeutic drugs knockdown yielded superior outcomes Together, our findings elucidate directly binds to enhancing thereby promoting may serve robust biomarker potential therapeutic target combination therapy

Язык: Английский

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