Alginate–marine collagen–agarose composite hydrogels as matrices for biomimetic 3D cell spheroid formation

Shin, Seung-Kuk; Ikram, Muhammad; Subhan, Fazli; Kang, Hae Yeong; Lim, Yeseon; Lee, Rira; Jin, Songwan; Jeong, Young Hun; Kwak, Jong‐Young; Na, Yong-Jin; Yoon, Sik

doi:10.1039/c6ra01937d

Cited by 64 publications

(49 citation statements)

References 54 publications

(56 reference statements)

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“…Composite hydrogels with an interpenetrating network structure formed by polysaccharides and proteins offered control over mechanical properties of the hydrogel and provided cell adhesion ligands, thus facilitating MCS growth ( 60 ). Recently, MCSs have been efficiently grown from human ovarian cancer cells in alginate-collagen-agarose hydrogels ( 61 ). Alginate has also been combined with Matrigel to investigate the malignant progression of normal mammary epithelium mediated by changing hydrogel stiffness ( 40 ).…”

Section: D Hydrogel Microenvironments For Mcs Growthmentioning

confidence: 99%

Hydrogel microenvironments for cancer spheroid growth and drug screening

2018

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Section: D Hydrogel Microenvironments For Mcs Growthmentioning

confidence: 99%

Hydrogel microenvironments for cancer spheroid growth and drug screening

2018

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“…[31] The artificial matrices used for the formation of 3D spheroids are usually produced by using non-adhesive polymers (e.g., agarose, hyaluronic acid (HA)) or a blend of non-adhesive polymers with other biomaterials. [32,33] The use of polymers with non-adhesive properties is essential to trigger the formation of spheroids. In this process, the adhesive forces among cells are more prominent than those established between the cells and the non-adhesive biomaterial, thus triggering the cellular aggregation.…”

Section: Introduction: Spheroids As 3d Tumor Tissue Culture Modelsmentioning

confidence: 99%

“…[33] Moreover, Shin and co-workers also developed alginate/collagen/agarose hydrogels to growth spheroids of ovarian carcinoma (A2780), lymphoblast (EL4), and epithelial (1308.1) cells. [32] Polymers are the most used materials to produce scaffold-based materials for 3D cell culture, as their chemical and structural properties can be optimized to fulfill the required properties. [34] Still, despite of the wide variety of scaffolds available for 3D cell culture, matrix supported spheroids production is mainly used for tissue engineering purposes, as these scaffold-based methods have demonstrated several drawbacks when drug screening applications are intended.…”

Section: Introduction: Spheroids As 3d Tumor Tissue Culture Modelsmentioning

confidence: 99%

Spheroids Formation on Non‐Adhesive Surfaces by Liquid Overlay Technique: Considerations and Practical Approaches

Costa

Melo‐Diogo

Moreira

et al. 2017

Biotechnology Journal

147

139

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Scalable and reproducible production of 3D cellular spheroids is highly demanded, by pharmaceutical companies, for drug screening purposes during the pre-clinical evaluation phase. These 3D cellular constructs, unlike the monolayer culture of cells, can mimic different features of human tissues, including cellular organization, cell-cell and cell-extracellular matrix (ECM) interactions. Up to now, different techniques (scaffold-based and -free) have been used for spheroids formation, being the Liquid Overlay Technique (LOT) one of the most explored methodologies, due to its low cost and easy handling. Additionally, during the last few decades, this technique has been widely investigated in order to enhance its potential for being applied in high-throughput analysis. Herein, an overview of the LOT advances, practical approaches, and troubleshooting is provided for those researchers that intend to produce spheroids using LOT, for drug screening purposes. Moreover, the advantages of the LOT over the other scaffold-free techniques used for the spheroids formation are also addressed. Highlights • 2D cell culture drawbacks are summarized;• spheroids mimic the features of human tissues;• scaffold-based and scaffold-free technologies for spheroids production are discussed; • advantages of LOT over other scaffold-free techniques are highlighted; • LOT advances, practical approaches and troubleshooting are underlined.

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“…Recent advances in cell biology, microfabrication techniques, and tissue engineering have enabled the development of a wide range of 3D cell culture technologies including multicellular spheroids, organoids, scaffolds, hydrogels, organs-on-chips, and 3D bioprinting, which are potentially useful to restore the morphological, functional, and microenvironmental features of human tissues and organs [ 5 ]. We recently reported the fabrication of a novel, physically gelated, bioactive, alginate/marine collagen/agarose (AmCA) composite hydrogel as a valuable matrix for biomimetic 3D cell spheroid formation and proposed its ability to efficiently create 3D multicellular spheroids for lymphoma cells [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Co-targeting of Tiam1/Rac1 and Notch ameliorates chemoresistance against doxorubicin in a biomimetic 3D lymphoma model

et al. 2017

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Lymphoma is a heterogeneous disease with a highly variable clinical course and prognosis. Improving the prognosis for patients with relapsed and treatment-resistant lymphoma remains challenging. Current in vitro drug testing models based on 2D cell culture lack natural tissue-like structural organization and result in disappointing clinical outcomes. The development of efficient drug testing models using 3D cell culture that more accurately reflects in vivo behaviors is vital. Our aim was to establish an in vitro 3D lymphoma model that can imitate the in vivo 3D lymphoma microenvironment. Using this model, we explored strategies to enhance chemosensitivity to doxorubicin, an important chemotherapeutic drug widely used for the treatment of hematological malignancies. Lymphoma cells grown in this model exhibited excellent biomimetic properties compared to conventional 2D culture including (1) enhanced chemotherapy resistance, (2) suppressed rate of apoptosis, (3) upregulated expression of drug resistance genes (MDR1, MRP1, BCRP and HIF-1α), (4) elevated levels of tumor aggressiveness factors including Notch (Notch-1, -2, -3, and -4) and its downstream molecules (Hes-1 and Hey-1), VEGF and MMPs (MMP-2 and MMP-9), and (5) enrichment of a lymphoma stem cell population. Tiam1, a potential biomarker of tumor progression, metastasis, and chemoresistance, was activated in our 3D lymphoma model. Remarkably, we identified two synergistic therapeutic oncotargets, Tiam1 and Notch, as a strategy to combat resistance against doxorubicin in EL4 T and A20 B lymphoma. Therefore, our data suggest that our 3D lymphoma model is a promising in vitro research platform for studying lymphoma biology and therapeutic approaches.

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Alginate–marine collagen–agarose composite hydrogels as matrices for biomimetic 3D cell spheroid formation

Abstract: We report a novel, customizable, transparent, biocompatible, functional, easy-to-produce, efficient and cost-effective AmCA scaffold for 3D cell culture.

Cited by 64 publications

References 54 publications

Hydrogel microenvironments for cancer spheroid growth and drug screening

Hydrogel microenvironments for cancer spheroid growth and drug screening

Spheroids Formation on Non‐Adhesive Surfaces by Liquid Overlay Technique: Considerations and Practical Approaches

Co-targeting of Tiam1/Rac1 and Notch ameliorates chemoresistance against doxorubicin in a biomimetic 3D lymphoma model

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