3D hydrogel-based microcapsules as an in vitro model to study tumorigenicity, cell migration and drug resistance

Ertekin, Özlem; Monavari, Mahshid; Krüger, René; Fuentes-Chandía, Miguel; Parma, Beatrice; Letort, Gaëlle; Tripal, Philipp; Boccaccını, Aldo R.; Boßerhoff, Anja; Ceppi, Paolo; Kappelmann‐Fenzl, Melanie; Leal‐Egaña, Aldo

doi:10.1016/j.actbio.2022.02.010

Cited by 22 publications

(15 citation statements)

References 76 publications

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“…Specifically, since it has the ability to create 3D porous structures in which cells can grow, this biomaterial can imitate in vivo microenvironment conditions. In fact, gelatin has been used to culture different cancer and stromal cells [80,102,103].…”

Section: In Vitro 3d Tissue Engineeringmentioning

confidence: 99%

Progress in Gelatin as Biomaterial for Tissue Engineering

et al. 2022

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Tissue engineering has become a medical alternative in this society with an ever-increasing lifespan. Advances in the areas of technology and biomaterials have facilitated the use of engineered constructs for medical issues. This review discusses on-going concerns and the latest developments in a widely employed biomaterial in the field of tissue engineering: gelatin. Emerging techniques including 3D bioprinting and gelatin functionalization have demonstrated better mimicking of native tissue by reinforcing gelatin-based systems, among others. This breakthrough facilitates, on the one hand, the manufacturing process when it comes to practicality and cost-effectiveness, which plays a key role in the transition towards clinical application. On the other hand, it can be concluded that gelatin could be considered as one of the promising biomaterials in future trends, in which the focus might be on the detection and diagnosis of diseases rather than treatment.

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Section: In Vitro 3d Tissue Engineeringmentioning

confidence: 99%

Progress in Gelatin as Biomaterial for Tissue Engineering

et al. 2022

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“…Cells were isolated from the microcapsules by immersing them in a solution containing of 22.5 mM of sodium citrate dihydrate, 60 mM EDTA and 150 mM of sodium chloride (Sigma-Aldrich; pH 7.4) for 1 minute, following protocols previously published. [28,29] After that, cells were isolated by centrifugation (1300 rpm, 4 min).…”

Section: Isolation Of Cells From Alginate-gelatin Microcapsulesmentioning

confidence: 99%

“…RNA extraction was carried out according to protocols already published. [28,29] All experiments were carried out in triplicate. 75 bps paired-end sequencing was performed on a HighSeq 4000 Sequencer (Illumina) with an average number of 20 million reads per (which was not certified by peer review) is the author/funder.…”

Section: Rna-seq Assays and Transcriptome Analysismentioning

confidence: 99%

“…To this purpose, the use of 3D polymer-based matrices, mimicking the most relevant properties of neoplastic niches, has emerged as a good alternative to fulfil this gap. In this regard, we recently published that the increased resistance of encapsulated MCF7 cancer cells to cisplatin, [28,29] seems to be due to the enhanced presence of polynucleated cells found in alginate-gelatin microcapsules (also known as tumor-like microcapsules in this (which was not certified by peer review) is the author/funder. All rights reserved.…”

Section: Introductionmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted September 23, 2022. ; https://doi.org/10.1101/2022.09.22.508846 doi: bioRxiv preprint manuscript). [28,29] However, the way how these polynucleated cells are increasing in number in absence of any external stimuli, and which 3D experimental system may exhibit advantages to study polyploidy in vitro, are still unsolved questions.…”

Section: Introductionmentioning

confidence: 99%

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When Mechanical Stress Matters: Generation of Polyploid Giant Cancer Cells in Tumor-like Microcapsules

Buehler

Krueger

Monavari

et al. 2022

Preprint

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In this work, we studied the generation and rising of polyploid cancer cells as a product of mechanical stress. To this purpose, MCF7 breast cancer cells were cultured on 2D (i.e. flasks, or flat hydrogels), and in 3D milieus (i.e. Spheroids, or immobilized within alginate-gelatin microbeads, named in this work as tumor-like microcapsules), and further analyzed by biophysical and genetic methods (i.e. single-cell Traction Force Microscopy and RNA-seq respectively). Our results show that MCF7 cells preconditioned onto 2D surfaces exhibit a low number of polynucleated cells, while their culture in 3D environments triggered their progressive generation with time. Genetic studies enabled us to determine that polyploid cells found in tumor-like microcapsules are likely originated by cell-cell fusion and disrupted cytokinesis, showing most of the genetic markers for Polyploid Giant Cancer Cell, while cells cultured as spheroids seem to be likely generated by other mechanisms, such as cell cannibalisms, entosis, or emperipolesis. Our outcomes strongly suggest that both mechanical stress and confinement are required to stimulate cell polyploidy, which can be easily addressed by the immobilization of breast cancer cells in tumor-like microcapsules.

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In Situ Fabrication of Constraints for Multicellular Micro‐Spheroids Using Two‐Photon Lithography

Taale,

Schamberger,

Taheri

et al. 2023

Adv Funct Materials

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Abstract2‐photon polymerization is a promising technology for creating complex, microscale 3D matrices for biomedical and also bioprinting applications. Cancer research provides compelling uses for this strategy, in particular, for generating a 3D constraint around multicellular spheroids. Because these spheroids are inhomogeneous in size and shape, the ability to target a spheroid composed of a few living cells requires geometrical control of the printing shape in situ. In this study, it is presented that two‐photon lithography can be used to study complex phenomena involved in cancer progression, such as collective 3D cell migration in situ in vitro. This method allows the spatial and temporal control of cancer cell migration from single spheroids, using dome‐shaped confinements with micrometer‐sized openings. The confinement of the spheroids leads to a decreased migration speed and affects actin dynamics. Furthermore, this methodology provides a novel way of analyzing the behavior of specific regions of multicellular structures, by enabling the separation of multicellular structures, while keeping them alive. Ultimately, this study demonstrates a new way to use two‐photon lithography for controlling the growth, migration and morphological cues of live cells, thus opening new avenues toward the dynamic in situ control of living 3D structures.

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3D hydrogel-based microcapsules as an in vitro model to study tumorigenicity, cell migration and drug resistance

Cited by 22 publications

References 76 publications

Progress in Gelatin as Biomaterial for Tissue Engineering

Progress in Gelatin as Biomaterial for Tissue Engineering

When Mechanical Stress Matters: Generation of Polyploid Giant Cancer Cells in Tumor-like Microcapsules

In Situ Fabrication of Constraints for Multicellular Micro‐Spheroids Using Two‐Photon Lithography

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