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The Effect of Hypoxic and Normoxic Culturing Conditions in Different Breast Cancer 3D Model Systems
University of Gothenburg, Sweden.
RISE Research Institutes of Sweden, Materials and Production, Product Realisation Methodology. University of Gothenburg, Sweden.ORCID iD: 0000-0002-8849-1793
University of Gothenburg, Sweden.
University of Gothenburg, Sweden.
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2021 (English)In: Frontiers in Bioengineering and Biotechnology, E-ISSN 2296-4185, Vol. 9, article id 711977Article in journal (Refereed) Published
Abstract [en]

The field of 3D cell cultures is currently emerging, and material development is essential in striving toward mimicking the microenvironment of a native tissue. By using the response of reporter cells to a 3D environment, a comparison between materials can be assessed, allowing optimization of material composition and microenvironment. Of particular interest, the response can be different in a normoxic and hypoxic culturing conditions, which in turn may alter the conclusion regarding a successful recreation of the microenvironment. This study aimed at determining the role of such environments to the conclusion of a better resembling cell culture model to native tissue. Here, the breast cancer cell line MCF7 was cultured in normoxic and hypoxic conditions on patient-derived scaffolds and compared at mRNA and protein levels to cells cultured on 3D printed scaffolds, Matrigel, and conventional 2D plastics. Specifically, a wide range of mRNA targets (40), identified as being regulated upon hypoxia and traditional markers for cell traits (cancer stem cells, epithelial–mesenchymal transition, pluripotency, proliferation, and differentiation), were used together with a selection of corresponding protein targets. 3D cultured cells were vastly different to 2D cultured cells in gene expression and protein levels on the majority of the selected targets in both normoxic and hypoxic culturing conditions. By comparing Matrigel and 3DPS-cultured cells to cells cultured on patient-derived scffolds, differences were also noted along all categories of mRNA targets while specifically for the GLUT3 protein. Overall, cells cultured on patient-derived scaffolds closely resembled cells cultured on 3D printed scaffolds, contrasting 2D and Matrigel-cultured cells, regardless of a normoxic or hypoxic culturing condition. Thus, these data support the use of either a normoxic or hypoxic culturing condition in assays using native tissues as a blueprint to optimize material composition. Copyright © 2021 Svanström, Rosendahl, Salerno, Jonasson, Håkansson, Ståhlberg and Landberg.

Place, publisher, year, edition, pages
Frontiers Media S.A. , 2021. Vol. 9, article id 711977
Keywords [en]
3D printed scaffolds (3DPS), alginate, breast cancer, hypoxia, normoxia, patient-derived scaffolds (PDS), 3D modeling, Cell culture, Diseases, Gene expression, Proteins, Scaffolds (biology), Stem cells, Tissue, 3d printed scaffold, Condition, Cultured cell, Material compositions, Microenvironments, Normoxium, Patient-derived scaffold, Protein level, 3D printers
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:ri:diva-57337DOI: 10.3389/fbioe.2021.711977Scopus ID: 2-s2.0-85120417220OAI: oai:DiVA.org:ri-57337DiVA, id: diva2:1622731
Note

Funding details: 716321, 721091; Funding details: Västra Götalandsregionen; Funding details: Stiftelsen för Strategisk Forskning, SSF, FID15-0008; Funding details: VINNOVA, 2017-03737; Funding details: Cancerfonden, 2019-0306, 2019-0317; Funding details: Vetenskapsrådet, VR, 2015-03256, 2016-01530, 2017-01392, 2019-01273; Funding details: Stiftelsen Assar Gabrielssons Fond, AG Fond; Funding text 1: This research was funded by Sweden’s Innovation Agency (2017-03737); the Swedish Cancer Society (2019-0306 and 2019-0317); the Swedish Research Council (2019-01273, 2017-01392, 2016-01530, and 2015-03256); the Swedish state under the agreement between the Swedish government and the county council, the ALF agreement (716321 and 721091); Region Västra Götaland, Sweden (RUN 2018-00017 and infrastructure support to AS), Swedish Foundation for Strategic Research (FID15-0008); Johan Jansson Foundation for Cancer Research; Wilhelm and Martina Lundgrens Foundation; Assar Gabrielsson Foundation; and the Foundation Sigurd och Elsa Goljes Minne.; Funding text 2: This research was funded by Sweden?s Innovation Agency (2017-03737); the Swedish Cancer Society (2019-0306 and 2019-0317); the Swedish Research Council (2019-01273, 2017-01392, 2016-01530, and 2015-03256); the Swedish state under the agreement between the Swedish government and the county council, the ALF agreement (716321 and 721091); Region V?stra G?taland, Sweden (RUN 2018-00017 and infrastructure support to AS), Swedish Foundation for Strategic Research (FID15-0008); Johan Jansson Foundation for Cancer Research; Wilhelm and Martina Lundgrens Foundation; Assar Gabrielsson Foundation; and the Foundation Sigurd och Elsa Goljes Minne.

Available from: 2021-12-23 Created: 2021-12-23 Last updated: 2023-05-22Bibliographically approved

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Rosendahl, JenniferHåkansson, Joakim

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