Scaffold-Free 3-D Cell Sheet Technique Bridges the Gap between 2-D Cell Culture and Animal Models

Alghuwainem, Ayidah; Alshareeda, Alaa T.; Al-Sowayan, Batla

doi:10.3390/ijms20194926

Cited by 57 publications

(50 citation statements)

References 54 publications

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“…Two of the main scaffolds used for three-dimensional cultures are hydrogel and polymer [ 5 ]. However, the limitations for scaffold-based systems include a greater immune response and the limitation of the loadable number of cells [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

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The Effects of Morinda citrifolia (Noni) on the Cellular Viability and Osteogenesis of Stem Cell Spheroids

Min

Park

2020

Medicina

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Background and objectives: Morinda citrifolia (Noni) has been widely used in herbal remedies to treat and prevent various kinds of diseases. We conducted this study to evaluate the effects of Noni extract on the maintenance of morphology, the improvement of cellular viability, and the enhancement of osteogenesis of stem cell spheroids. Materials and Methods: We cultured stem cell spheroids made with gingiva-derived stem cells in the presence of Noni extract at concentrations of 10, 100 and 200 ng/mL. We performed analysis of the cell morphology and changes in the cellular viability. We conducted alkaline phosphatase activity assays using a kit, and mineralization assays using an anthraquinone dye to evaluate the osteogenesis of stem cell spheroids with the addition of Noni extract. Results: The applied cells formed spheroids well, and the addition of Noni at 10, 100 and 200 ng/mL concentrations did not produce significant morphological changes. The quantitative values for cellular viability on Day 3 showed that the absorbance values at 450 nm were 0.314 ± 0.013, 0.318 ± 0.008, 0.304 ± 0.000 and 0.300 ± 0.011 for Noni at 0, 10, 100 and 200 ng/mL concentrations, respectively. The results of alkaline phosphatase activity with absorbance values at 405 nm were 0.189 ± 0.019, 0.174 ± 0.023, 0.192 ± 0.014 and 0.210 ± 0.062 for Noni at 0, 10, 100 and 200 ng/mL concentrations, respectively, on Day 4. There were significantly higher values of Alizarin Red S staining for Noni in the 10, 100 and 200 ng/mL groups, with the highest value at 100 ng/mL when compared with the unloaded control on Day 14. Conclusions: Based on these findings, we concluded that Noni extract might be applied for the enhanced osteogenic differentiation of stem cell spheroids.

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Section: Introductionmentioning

confidence: 99%

“…Recently, scaffold-free techniques have been of great interest because this technique allows the various types of cells, including stem cells, to form cell aggregates called spheroids [ 6 , 7 ]. Spheroids can be fabricated in various sizes and shapes, and the reproducible size/shape of spheroids can be obtained [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

The Effects of Morinda citrifolia (Noni) on the Cellular Viability and Osteogenesis of Stem Cell Spheroids

Min

Park

2020

Medicina

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“…Two subcategories emerge from this discipline: Solid scaffold-based technology that provides a 3D space hosting cells and allowing them to create 3D tissue-like structures. Natural or synthetic, they consist of porous membranes or fibrous scaffolds that have been widely studied in the field of stem cells and regenerative medicine, for example, porous membranes produced by thermally induced phase separation [ 28 , 29 ]. Owing to their porous structure, these 3D matrixes facilitate tissue regeneration (e.g., cornea, skin and bone) [ 30 , 31 , 32 ].…”

Section: Three-dimensional Culture Systemsmentioning

confidence: 99%

Biomaterials for Three-Dimensional Cell Culture: From Applications in Oncology to Nanotechnology

et al. 2021

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Three-dimensional cell culture has revolutionized cellular biology research and opened the door to novel discoveries in terms of cellular behavior and response to microenvironment stimuli. Different types of 3D culture exist today, including hydrogel scaffold-based models, which possess a complex structure mimicking the extracellular matrix. These hydrogels can be made of polymers (natural or synthetic) or low-molecular weight gelators that, via the supramolecular assembly of molecules, allow the production of a reproducible hydrogel with tunable mechanical properties. When cancer cells are grown in this type of hydrogel, they develop into multicellular tumor spheroids (MCTS). Three-dimensional (3D) cancer culture combined with a complex microenvironment that consists of a platform to study tumor development and also to assess the toxicity of physico-chemical entities such as ions, molecules or particles. With the emergence of nanoparticles of different origins and natures, implementing a reproducible in vitro model that consists of a bio-indicator for nano-toxicity assays is inevitable. However, the maneuver process of such a bio-indicator requires the implementation of a repeatable system that undergoes an exhaustive follow-up. Hence, the biggest challenge in this matter is the reproducibility of the MCTS and the associated full-scale characterization of this system’s components.

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“…The scaffold-free methods, relying on external forces for cell aggregation, take advantage of cell–cell interaction to create dense cell aggregates. Relying on cell–cell contact during MCTS formation greatly reduces time until the scaffold-free MCTSs are physiologically relevant models for solid tumors due to high initial cell density [ 10 ]. The most extensively used external force is gravity which in combination with low-adhesion surfaces or hanging drops forms MCTSs [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Ultrasound-Based Scaffold-Free Core-Shell Multicellular Tumor Spheroid Formation

et al. 2021

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In cancer research and drug screening, multicellular tumor spheroids (MCTSs) are a popular model to bridge the gap between in vitro and in vivo. However, the current techniques to culture mixed co-culture MCTSs do not mimic the structural architecture and cellular spatial distribution in solid tumors. In this study we present an acoustic trapping-based core-shell MCTSs culture method using sequential seeding of the core and shell cells into microwells coated with a protein repellent coating. Scaffold-free core-shell ovarian cancer OVCAR-8 cell line MCTSs were cultured, stained, cleared and confocally imaged on-chip. Image analysis techniques were used to quantify the shell thickness (23.2 ± 1.8 µm) and shell coverage percentage (91.2 ± 2.8%). We also show that the shell thickness was evenly distributed over the MCTS cores with the exception of being slightly thinner close to the microwell bottom. This scaffold-free core-shell MCTSs formation technique and the analysis tools presented herein could be used as an internal migration assay within the MCTS or to form core-shell MCTS co-cultures to study therapy response or the interaction between tumor and stromal cells.

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Scaffold-Free 3-D Cell Sheet Technique Bridges the Gap between 2-D Cell Culture and Animal Models

Cited by 57 publications

References 54 publications

The Effects of Morinda citrifolia (Noni) on the Cellular Viability and Osteogenesis of Stem Cell Spheroids

The Effects of Morinda citrifolia (Noni) on the Cellular Viability and Osteogenesis of Stem Cell Spheroids

Biomaterials for Three-Dimensional Cell Culture: From Applications in Oncology to Nanotechnology

Ultrasound-Based Scaffold-Free Core-Shell Multicellular Tumor Spheroid Formation

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