Multicellular tumor spheroids in microcapsules as a novel 3D in vitro model in tumor biology

Presently multicellular tumor spheroids (MTS) are being widely used in various aspects of tumor biology, including studies in biology and photodynamic therapy. The cellular organization of spheroids allows the recreation of in vivo small tumors much better than all common two-dimensional in vitro models. The cell encapsulation method could be proposed as a novel technique to quickly and easily prepare a large number of spheroids with narrow size distribution within a desirable diameter range. Moreover, the proposed technique for spheroid generation using encapsulated growing tumor cells could provide entirely new avenues to develop a novel spheroid co-culture model (for instance, the in vitro co-cultvation of tumor cells and monocytes, or epithelial cells, or fibroblasts etc). The current research was aimed at developing a simple and reliable method to encapsulate tumor cells and to cultivate them in vitro. In order to generate spheroids, MCF-7 cells were encapsulated and cultivated in 200 ml T-flasks in a 5% CO2 atmosphere at 37?C for 4-5 weeks. The cell proliferation was easily observed using a light microscope. The cells grew in aggregates increasing in size with time. The cell growth resulted in the formation of large cell clusters (spheroids) which filled the whole microcapsule volume in 4-5 weeks.

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Microencapsulated multicellular tumor spheroids as a novel in vitro model for drug screening

Biochemistry (Moscow) Supplement Series B Biomedical Chemistry ◽

10.1134/s1990750810030054 ◽

2010 ◽

Vol 4 (3) ◽

pp. 243-250 ◽

Cited By ~ 4

Author(s):

A. M. Tsoy ◽

D. S. Zaytseva-Zotova ◽

E. F. Edelweiss ◽

A. Bartkowiak ◽

J. -L. Goergen ◽

...

Keyword(s):

Drug Screening ◽

In Vitro Model ◽

Multicellular Tumor Spheroids ◽

Tumor Spheroids ◽

Vitro Model

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Engineering a 3D in vitro model of human skeletal muscle at the single fiber scale

PLoS ONE ◽

10.1371/journal.pone.0232081 ◽

2020 ◽

Vol 15 (5) ◽

pp. e0232081 ◽

Cited By ~ 2

Author(s):

Anna Urciuolo ◽

Elena Serena ◽

Rusha Ghua ◽

Susi Zatti ◽

Monica Giomo ◽

...

Keyword(s):

Skeletal Muscle ◽

Human Skeletal Muscle ◽

In Vitro Model ◽

Single Fiber ◽

3D In Vitro Model ◽

Vitro Model

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Of mice and men: Mechanistic studies on the developmental neurotoxicity of polybrominated diphenyl ethers (PBDES) in a 3D in vitro model

Toxicology Letters ◽

10.1016/j.toxlet.2014.06.424 ◽

2014 ◽

Vol 229 ◽

pp. S118

Author(s):

Katharina Dach ◽

Henrik Alm ◽

Susanne Giersiefer ◽

Ellen Fritsche

Keyword(s):

Polybrominated Diphenyl Ethers ◽

In Vitro Model ◽

Developmental Neurotoxicity ◽

Mechanistic Studies ◽

3D In Vitro Model ◽

Diphenyl Ethers ◽

Of Mice And Men ◽

Vitro Model

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A 3D in vitro model of the dermoepidermal junction amenable to mechanical testing

Journal of Biomedical Materials Research Part A ◽

10.1002/jbm.a.36519 ◽

2018 ◽

Vol 106 (12) ◽

pp. 3231-3238 ◽

Cited By ~ 3

Author(s):

Jangwook P. Jung ◽

Wei-Han Lin ◽

Megan J. Riddle ◽

Jakub Tolar ◽

Brenda M. Ogle

Keyword(s):

Mechanical Testing ◽

In Vitro Model ◽

Dermoepidermal Junction ◽

3D In Vitro Model ◽

Vitro Model

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Polyurethane foam scaffolds: a novel 3D in vitro model for breast cancer-derived bone metastasis

Frontiers in Bioengineering and Biotechnology ◽

10.3389/conf.fbioe.2016.01.00915 ◽

2016 ◽

Vol 4 ◽

Author(s):

Contessi Nicola ◽

Angeloni Valentina ◽

De Marco Cinzia ◽

Tanzi Maria Cristina ◽

Daidone Maria Grazia ◽

...

Keyword(s):

Breast Cancer ◽

Bone Metastasis ◽

Polyurethane Foam ◽

In Vitro Model ◽

3D In Vitro Model ◽

Vitro Model

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Human stem cell-derived cardiac spheroids as 3D in vitro model for cardiotoxicity testing

Journal of Pharmacological and Toxicological Methods ◽

10.1016/j.vascn.2020.106848 ◽

2020 ◽

Vol 105 ◽

pp. 106848

Author(s):

Ki-Suk Kim

Keyword(s):

Stem Cell ◽

In Vitro Model ◽

Human Stem Cell ◽

3D In Vitro Model ◽

Vitro Model

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CAFs affect the proliferation and treatment response of head and neck cancer spheroids during co-culturing in a unique in vitro model

Cancer Cell International ◽

10.1186/s12935-020-01718-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Mustafa Magan ◽

Emilia Wiechec ◽

Karin Roberg

Keyword(s):

Cell Proliferation ◽

Tumor Cell ◽

Head And Neck ◽

Treatment Response ◽

Tumor Cells ◽

In Vitro Model ◽

Tumor Spheroids ◽

Vitro Model ◽

The Impact

Abstract Background Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors for which the overall survival rate worldwide is around 60%. The tumor microenvironment, including cancer-associated fibroblasts (CAFs), is believed to affect the treatment response and migration of HNSCC. The aim of this study was to create a biologically relevant HNSCC in vitro model consisting of both tumor cells and CAFs cultured in 3D to establish predictive biomarkers for treatment response, as well as to investigate the impact of CAFs on phenotype, proliferation and treatment response in HNSCC cells. Methods Three different HNSCC patient-derived tumor cell lines were cultured with and without CAFs in a 3D model. Immunohistochemistry of the proliferation marker Ki67, epidermal growth factor receptor (EGFR) and fibronectin and a TUNEL-assay were performed to analyze the effect of CAFs on both tumor cell proliferation and response to cisplatin and cetuximab treatment in tumor spheroids (3D). mRNA expression of epithelial-mesenchymal transition (EMT) and cancer stem cells markers were analyzed using qRT-PCR. Results The results demonstrated increased cell proliferation within the tumor spheroids in the presence of CAFs, correlating with increased expression of EGFR. In spheroids with increased expression of EGFR, a potentiated response to cetuximab treatment was observed. Surprisingly, an increase in Ki67 expressing tumor cells were observed in spheroids treated with cisplatin for 3 days, correlating with increased expression of EGFR. Furthermore, tumor cells co-cultured with CAFs presented an increased EMT phenotype compared to tumor cells cultured alone in 3D. Conclusion Taken together, our results reveal increased cell proliferation and elevated expression of EGFR in HNSCC tumor spheroids in the presence of CAFs. These results, together with the altered EMT phenotype, may influence the response to cetuximab or cisplatin treatment.

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