Macromolecular crowding in the development of a three-dimensional organotypic human breast cancer model

Shologu, Naledi; Gürdal, Mehmet; Szegezdi, Éva; FitzGerald, Una; Zeugolis, Dimitrios I.

doi:10.1016/j.biomaterials.2022.121642

Cited by 5 publications

(3 citation statements)

References 118 publications

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“…Owing to the importance of the biophysical microenvironment of the tumour ECM in regulating various aspects of cancer cell behaviour including, migration, proliferation and drug resistance [ 28 , 100 ], CDMs represent physiologically relevant and more controllable models for fundamental research on cancer as well as for screening or testing antitumoral drugs. Several matrices derived from either tumour cells or non-tumour cells have been proposed for a variety of tumours, including oral cancer [ 101 ], breast cancer [ 102 , 103 ], myeloma bone disease [ 104 ], ovarian cancer and colorectal cancer [ 105 , 106 ]. Increased proliferation and drug resistance have been frequently reported in cases of tumour cells cultivated in CDMs with respect to cells grown on tissue culture plastic [ 103 , 107 , 108 ].…”

Section: Cell Derived Matricesmentioning

confidence: 99%

“…Several matrices derived from either tumour cells or non-tumour cells have been proposed for a variety of tumours, including oral cancer [ 101 ], breast cancer [ 102 , 103 ], myeloma bone disease [ 104 ], ovarian cancer and colorectal cancer [ 105 , 106 ]. Increased proliferation and drug resistance have been frequently reported in cases of tumour cells cultivated in CDMs with respect to cells grown on tissue culture plastic [ 103 , 107 , 108 ]. In particular, the differences in cell behaviour and response to drugs have been linked to the stiffer matrices produced by tumour or tumour-associated cells [ 107 , 109 ].…”

Section: Cell Derived Matricesmentioning

confidence: 99%

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Collagen-Based Biomimetic Systems to Study the Biophysical Tumour Microenvironment

Cambi

Ventre

2022

Cancers

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The extracellular matrix (ECM) is a pericellular network of proteins and other molecules that provides mechanical support to organs and tissues. ECM biophysical properties such as topography, elasticity and porosity strongly influence cell proliferation, differentiation and migration. The cell’s perception of the biophysical microenvironment (mechanosensing) leads to altered gene expression or contractility status (mechanotransduction). Mechanosensing and mechanotransduction have profound implications in both tissue homeostasis and cancer. Many solid tumours are surrounded by a dense and aberrant ECM that disturbs normal cell functions and makes certain areas of the tumour inaccessible to therapeutic drugs. Understanding the cell-ECM interplay may therefore lead to novel and more effective therapies. Controllable and reproducible cell culturing systems mimicking the ECM enable detailed investigation of mechanosensing and mechanotransduction pathways. Here, we discuss ECM biomimetic systems. Mainly focusing on collagen, we compare and contrast structural and molecular complexity as well as biophysical properties of simple 2D substrates, 3D fibrillar collagen gels, cell-derived matrices and complex decellularized organs. Finally, we emphasize how the integration of advanced methodologies and computational methods with collagen-based biomimetics will improve the design of novel therapies aimed at targeting the biophysical and mechanical features of the tumour ECM to increase therapy efficacy.

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Section: Cell Derived Matricesmentioning

confidence: 99%

Section: Cell Derived Matricesmentioning

confidence: 99%

Collagen-Based Biomimetic Systems to Study the Biophysical Tumour Microenvironment

Cambi

Ventre

2022

Cancers

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“…In a diverse range of permanently differentiated and mesenchymal stomal cell culture systems, MMC (i.e., the addition of macromolecules in culture media) has been shown to enhance and accelerate extracellular matrix (ECM) deposition [18,19]. As a direct consequence, tissue engineered medicines [20] and cell derived matrices for cell expansion [21], drug discovery [22], and reparative [23] purposes with superior to the state-of-the-art functionality can now be developed using only a fraction cells and time that traditional approaches require.…”

Section: Introductionmentioning

confidence: 99%

Gums as Macromolecular Crowding Agents in Human Skin Fibroblast Cultures

Guillaumin,

Gurdal,

Zeugolis

2024

Life

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Even though tissue-engineered medicines are under intense academic, clinical, and commercial investigation, only a handful of products have been commercialised, primarily due to the costs associated with their prolonged manufacturing. While macromolecular crowding has been shown to enhance and accelerate extracellular matrix deposition in eukaryotic cell culture, possibly offering a solution in this procrastinating tissue-engineered medicine development, there is still no widely accepted macromolecular crowding agent. With these in mind, we herein assessed the potential of gum Arabic, gum gellan, gum karaya, and gum xanthan as macromolecular crowding agents in WS1 skin fibroblast cultures (no macromolecular crowding and carrageenan were used as a control). Dynamic light scattering analysis revealed that all macromolecules had negative charge and were polydispersed. None of the macromolecules affected basic cellular function. At day 7 (the longest time point assessed), gel electrophoresis analysis revealed that all macromolecules significantly increased collagen type I deposition in comparison to the non-macromolecular crowding group. Also at day 7, immunofluorescence analysis revealed that carrageenan; the 50 µg/mL, 75 µg/mL, and 100 µg/mL gum gellan; and the 500 µg/mL and 1000 µg/mL gum xanthan significantly increased both collagen type I and collagen type III deposition and only carrageenan significantly increased collagen type V deposition, all in comparison to the non-macromolecular crowding group at the respective time point. This preliminary study demonstrates the potential of gums as macromolecular crowding agents, but more detailed biological studies are needed to fully exploit their potential in the development of tissue-engineered medicines.

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Macromolecular crowding in equine bone marrow mesenchymal stromal cell cultures using single and double hyaluronic acid macromolecules

Garnica-Galvez,

Skoufos,

Tzora

et al. 2023

Acta Biomaterialia

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Macromolecular crowding in the development of a three-dimensional organotypic human breast cancer model

Cited by 5 publications

References 118 publications

Collagen-Based Biomimetic Systems to Study the Biophysical Tumour Microenvironment

Collagen-Based Biomimetic Systems to Study the Biophysical Tumour Microenvironment

Gums as Macromolecular Crowding Agents in Human Skin Fibroblast Cultures

Macromolecular crowding in equine bone marrow mesenchymal stromal cell cultures using single and double hyaluronic acid macromolecules

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