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Fluid and Bubble Flow Detach Adherent Cancer Cells to Form Spheroids on a Random Positioning Machine

Cortés-Sánchez, J.L. and Melnik, D. and Sandt, V. and Kahlert, S. and Marchal, S. and Johnson, I. and Calvaruso, M. and Liemersdorf, C. and Wuest, S. and Grimm, D. and Krüger, M. (2023) Fluid and Bubble Flow Detach Adherent Cancer Cells to Form Spheroids on a Random Positioning Machine. Cells, 12 (22), p. 2665. Multidisciplinary Digital Publishing Institute (MDPI). doi: 10.3390/cells12222665. ISSN 2073-4409.

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Official URL: https://doi.org/10.3390/cells12222665

Abstract

In preparing space and microgravity experiments, the utilization of ground-based facilities is common for initial experiments and feasibility studies. One approach to simulating microgravity conditions on Earth is to employ a random positioning machine (RPM) as a rotary bioreactor. Combined with a suitable low-mass model system, such as cell cultures, these devices simulating microgravity have been shown to produce results similar to those obtained in a space experiment under real microgravity conditions. One of these effects observed under real and simulated microgravity is the formation of spheroids from 2D adherent cancer cell cultures. Since real microgravity cannot be generated in a laboratory on Earth, we aimed to determine which forces lead to the detachment of individual FTC-133 thyroid cancer cells and the formation of tumor spheroids during culture with exposure to random positioning modes. To this end, we subdivided the RPM motion into different static and dynamic orientations of cell culture flasks. We focused on the molecular activation of the mechanosignaling pathways previously associated with spheroid formation in microgravity. Our results suggest that RPM-induced spheroid formation is a two-step process. First, the cells need to be detached, induced by the cell culture flask’s rotation and the subsequent fluid flow, as well as the presence of air bubbles. Once the cells are detached and in suspension, random positioning prevents sedimentation, allowing 3D aggregates to form. In a comparative shear stress experiment using defined fluid flow paradigms, transcriptional responses were triggered comparable to exposure of FTC-133 cells to the RPM. In summary, the RPM serves as a simulator of microgravity by randomizing the impact of Earth’s gravity vector especially for suspension (i.e., detached) cells. Simultaneously, it simulates physiological shear forces on the adherent cell layer. The RPM thus offers a unique combination of environmental conditions for in vitro cancer research.

Item URL in elib:https://elib.dlr.de/202872/
Document Type:Article
Title:Fluid and Bubble Flow Detach Adherent Cancer Cells to Form Spheroids on a Random Positioning Machine
Authors:
AuthorsInstitution or Email of AuthorsAuthor's ORCID iDORCID Put Code
Cortés-Sánchez, J.L.Department of Microgravity and Translational Regenerative Medicine, Otto-von-Guericke University, 39106 Magdeburg, GermanyUNSPECIFIEDUNSPECIFIED
Melnik, D.Department of Microgravity and Translational Regenerative Medicine, Otto-von-Guericke University, 39106 Magdeburg, Germanyhttps://orcid.org/0009-0006-5989-2906153576978
Sandt, V.Department of Microgravity and Translational Regenerative Medicine, Otto-von-Guericke University, 39106 Magdeburg, GermanyUNSPECIFIEDUNSPECIFIED
Kahlert, S.Institute of Anatomy, University Hospital Magdeburg, 39120 Magdeburg, GermanyUNSPECIFIEDUNSPECIFIED
Marchal, S.Department of Microgravity and Translational Regenerative Medicine, Otto-von-Guericke University, 39106 Magdeburg, GermanyUNSPECIFIEDUNSPECIFIED
Johnson, I.Research in Space Environments Group, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaUNSPECIFIEDUNSPECIFIED
Calvaruso, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liemersdorf, C.Gravitational Biology, Institute of Aerospace Medicine, German Aerospace Centre (DLR), Cologne, Germanyhttps://orcid.org/0000-0001-8407-5226UNSPECIFIED
Wuest, S.School of Engineering and Architecture, CC Aerospace Biomedical Science and Technology, Space Biology Group, Lucerne University of Applied Sciences and Arts, Hergiswil, SwitzerlandUNSPECIFIEDUNSPECIFIED
Grimm, D.Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, Aarhus C, DK-8000, DenmarkUNSPECIFIEDUNSPECIFIED
Krüger, M.Department of Microgravity and Translational Regenerative Medicine, Otto-von-Guericke University, 39106 Magdeburg, GermanyUNSPECIFIEDUNSPECIFIED
Date:20 November 2023
Journal or Publication Title:Cells
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:12
DOI:10.3390/cells12222665
Page Range:p. 2665
Editors:
EditorsEmailEditor's ORCID iDORCID Put Code
Kalyuzhny, AUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Publisher:Multidisciplinary Digital Publishing Institute (MDPI)
ISSN:2073-4409
Status:Published
Keywords:rotating bioreactor; simulated microgravity; cancer cell; shear stress; cell detachment; in vitro metastasis
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Research under Space Conditions
DLR - Research theme (Project):R - Gravisensorics
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine
Institute of Aerospace Medicine > Gravitational Biology
Deposited By: Anken, Ralf
Deposited On:20 Feb 2024 07:58
Last Modified:26 Feb 2024 11:48

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