Adaptable stirred-tank culture strategies for large scale production of multicellular spheroid-based tumor cell models

Santo, Vítor E.; Estrada, Marta; Rebelo, Sérgio; Abreu, Sofia; Silva, Inês; Pinto, Catarina; Veloso, S.; Serra, Ana Teresa; Boghaert, Erwin R.; Alves, Paula M.; Brito, Catarina

doi:10.1016/j.jbiotec.2016.01.031

Cited by 92 publications

(103 citation statements)

References 63 publications

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“…Agitation frequency or spinner velocity, as well as cell density, are significant variables in this method of spheroid formation. As reported by Santo et al [42] and Nyberg et al [46] as agitation frequency increased, smaller spheroids were generated. However, the agitation or stirring rate must be kept above a specific value to hinder cell sedimentation during the spheroid formation process.…”

Section: Bioreactor Flasksmentioning

confidence: 52%

“…There are several methods for cell spheroid formation other than the microfluidic approach including magnetic levitation [34], 3D-bioprinting [35], hydrophobic surfaces [36], matrix-on-top [37], matrix-embedded [38], polymeric aqueous two-phase system [39], floating liquid marbles [40], multiwell plates [41], bioreactor flasks [42], liquid overlay [43] and HD techniques [36]. Some of these techniques such as HD and multiwell plates are laborious while some others like 3D-bioprinting and magnetic levitation are costly and still lack the standard protocols.…”

Section: Conventional Methods For Spheroid Formationmentioning

confidence: 99%

“…However, these devices are not suitable for drug screening since they require a high content of drug and culture media and also cannot mimic the in vivo microenvironment [45]. Thus, for this purpose spheroids must be retrieved and put into other culture platforms such as the multiwell plates [42] or microfluidic spheroid culture chips (µSCCs).…”

Section: Bioreactor Flasksmentioning

confidence: 99%

“…In the bioreactor, cell aggregates of various diameters are formed after a given time, depending on the type of the cell line and the bioreactor physical features such as speed of stirring [42]. Spheroids may be formed first by other methods and then placed into a bioreactor for culturing [45].…”

Section: Bioreactor Flasksmentioning

confidence: 99%

“…Spheroids may be formed first by other methods and then placed into a bioreactor for culturing [45]. Santo et al [42] recently developed an adaptable stirred-tank bioreactor culture strategy to perform high throughput spheroid formation (HTSF). Agitation frequency or spinner velocity, as well as cell density, are significant variables in this method of spheroid formation.…”

Section: Bioreactor Flasksmentioning

confidence: 99%

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Inventions and Innovations in Preclinical Platforms for Cancer Research

2018

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Three-dimensional (3D) cell culture systems can be regarded as suitable platforms to bridge the huge gap between animal studies and two-dimensional (2D) monolayer cell culture to study chronic diseases such as cancer. In particular, the preclinical platforms for multicellular spheroid formation and culture can be regarded as ideal in vitro tumour models. The complex tumour microenvironment such as hypoxic region and necrotic core can be recapitulated in 3D spheroid configuration. Cells aggregated in spheroid structures can better illustrate the performance of anti-cancer drugs as well. Various methods have been proposed so far to create such 3D spheroid aggregations. Both conventional techniques and microfluidic methods can be used for generation of multicellular spheroids. In this review paper, we first discuss various spheroid formation phases. Then, the conventional spheroid formation techniques such as bioreactor flasks, liquid overlay and hanging droplet technique are explained. Next, a particular topic of the hydrogel in spheroid formation and culture is explored. This topic has received less attention in the literature. Hydrogels entail some advantages to the spheroid formation and culture such as size uniformity, the formation of porous spheroids or hetero-spheroids as well as chemosensitivity and invasion assays and protecting from shear stress. Finally, microfluidic methods for spheroid formation and culture are briefly reviewed.

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Section: Bioreactor Flasksmentioning

confidence: 52%

Section: Conventional Methods For Spheroid Formationmentioning

confidence: 99%

Section: Bioreactor Flasksmentioning

confidence: 99%

Section: Bioreactor Flasksmentioning

confidence: 99%

Section: Bioreactor Flasksmentioning

confidence: 99%

See 3 more Smart Citations

Inventions and Innovations in Preclinical Platforms for Cancer Research

2018

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Advanced Methods for Design of Scaffolds for 3D Cell Culturing

Vihar

Milojević

Banović³

et al. 2023

Functional Biomaterials

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Cancer Stem Cells in Tumor Modeling: Challenges and Future Directions

Dogan

Kısım

Bati-Ayaz

et al. 2021

Advanced NanoBiomed Research

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Microfluidic tumors‐on‐chips models have revolutionized anticancer therapeutic research by creating an ideal microenvironment for cancer cells. The tumor microenvironment (TME) includes various cell types and cancer stem cells (CSCs), which are postulated to regulate the growth, invasion, and migratory behavior of tumor cells. In this review, the biological niches of the TME and cancer cell behavior focusing on the behavior of CSCs are summarized. Conventional cancer models such as 3D cultures and organoid models are reviewed. Opportunities for the incorporation of CSCs with tumors‐on‐chips are then discussed for creating tumor invasion models. Such models will represent a paradigm shift in the cancer community by allowing oncologists and clinicians to predict better which cancer patients will benefit from chemotherapy treatments.

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Adaptable stirred-tank culture strategies for large scale production of multicellular spheroid-based tumor cell models

Cited by 92 publications

References 63 publications

Inventions and Innovations in Preclinical Platforms for Cancer Research

Inventions and Innovations in Preclinical Platforms for Cancer Research

Advanced Methods for Design of Scaffolds for 3D Cell Culturing

Cancer Stem Cells in Tumor Modeling: Challenges and Future Directions

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