Growth of Endothelial Cells in Space and in Simulated Microgravity - a Comparison on the Secretory Level.


Journal

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
ISSN: 1421-9778
Titre abrégé: Cell Physiol Biochem
Pays: Germany
ID NLM: 9113221

Informations de publication

Date de publication:
2019
Historique:
received: 21 08 2018
accepted: 17 01 2019
entrez: 13 4 2019
pubmed: 13 4 2019
medline: 3 5 2019
Statut: ppublish

Résumé

Endothelial cells exposed to the Random Positioning Machine (RPM) reveal three different phenotypes. They grow as a two-dimensional monolayer and form three-dimensional (3D) structures such as spheroids and tubular constructs. As part of the ESA-SPHEROIDS project we want to understand how endothelial cells (ECs) react and adapt to long-term microgravity. During a spaceflight to the International Space Station (ISS) and a subsequent stay onboard, human ECs (EA.hy926 cell line) were cultured for 12 days in real microgravity inside an automatic flight hardware, specially designed for use in space. ECs were cultivated in the absence or presence of vascular endothelial growth factor, which had demonstrated a cell-protective effect on ECs exposed to an RPM simulating microgravity. After cell fixation in space and return of the samples, we examined cell morphology and analyzed supernatants by Multianalyte Profiling technology. The fixed samples comprised 3D multicellular spheroids and tube-like structures in addition to monolayer cells, which are exclusively observed during growth under Earth gravity (1g). Within the 3D aggregates we detected enhanced collagen and laminin. The supernatant analysis unveiled alterations in secretion of several growth factors, cytokines, and extracellular matrix components as compared to cells cultivated at 1g or on the RPM. This confirmed an influence of gravity on interacting key proteins and genes and demonstrated a flight hardware impact on the endothelial secretome. Since formation of tube-like aggregates was observed only on the RPM and during spaceflight, we conclude that microgravity may be the major cause for ECs' 3D aggregation.

Sections du résumé

BACKGROUND/AIMS OBJECTIVE
Endothelial cells exposed to the Random Positioning Machine (RPM) reveal three different phenotypes. They grow as a two-dimensional monolayer and form three-dimensional (3D) structures such as spheroids and tubular constructs. As part of the ESA-SPHEROIDS project we want to understand how endothelial cells (ECs) react and adapt to long-term microgravity.
METHODS METHODS
During a spaceflight to the International Space Station (ISS) and a subsequent stay onboard, human ECs (EA.hy926 cell line) were cultured for 12 days in real microgravity inside an automatic flight hardware, specially designed for use in space. ECs were cultivated in the absence or presence of vascular endothelial growth factor, which had demonstrated a cell-protective effect on ECs exposed to an RPM simulating microgravity. After cell fixation in space and return of the samples, we examined cell morphology and analyzed supernatants by Multianalyte Profiling technology.
RESULTS RESULTS
The fixed samples comprised 3D multicellular spheroids and tube-like structures in addition to monolayer cells, which are exclusively observed during growth under Earth gravity (1g). Within the 3D aggregates we detected enhanced collagen and laminin. The supernatant analysis unveiled alterations in secretion of several growth factors, cytokines, and extracellular matrix components as compared to cells cultivated at 1g or on the RPM. This confirmed an influence of gravity on interacting key proteins and genes and demonstrated a flight hardware impact on the endothelial secretome.
CONCLUSION CONCLUSIONS
Since formation of tube-like aggregates was observed only on the RPM and during spaceflight, we conclude that microgravity may be the major cause for ECs' 3D aggregation.

Identifiants

pubmed: 30977987
doi: 10.33594/000000071
doi:

Types de publication

Comparative Study Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1039-1060

Subventions

Organisme : German Space Agency
ID : 50BW1124, 50BW1524
Pays : Germany
Organisme : European Space Agency
ID : ESA-AO-2004-006
Pays : Germany
Organisme : PROgramme for the Development of scientific Experiments (PRODEX), European Space Agency
ID : 4000109861
Pays : Belgium

Informations de copyright

© Copyright by the Author(s). Published by Cell Physiol Biochem Press.

Déclaration de conflit d'intérêts

Competing financial interests: The authors declare no competing financial interests. The views expressed herein can in no way be taken to reflect the official opinion of the European Space Agency.

Auteurs

Marcus Krüger (M)

Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University Magdeburg, Magdeburg, Germany.

Jessica Pietsch (J)

Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University Magdeburg, Magdeburg, Germany.

Johann Bauer (J)

Max Planck Institute of Biochemistry, Martinsried, Germany.

Sascha Kopp (S)

Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University Magdeburg, Magdeburg, Germany.

Daniel T O Carvalho (DTO)

Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University Magdeburg, Magdeburg, Germany.

Sarah Baatout (S)

Radiobiology Unit, Belgian Nuclear Research Centre, Mol, Belgium.
Molecular Biotechnology, Ghent University, Ghent, Belgium.

Marjan Moreels (M)

Radiobiology Unit, Belgian Nuclear Research Centre, Mol, Belgium.

Daniela Melnik (D)

Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University Magdeburg, Magdeburg, Germany.

Markus Wehland (M)

Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University Magdeburg, Magdeburg, Germany.

Marcel Egli (M)

Institute of Medical Engineering, Space Biology Group, Lucerne University of Applied Sciences and Arts, Hergiswil, Switzerland.

Sahana Jayashree (S)

Department of Biomedicine, Aarhus University, Aarhus, Denmark.

Sara Dam Kobberø (SD)

Department of Biomedicine, Aarhus University, Aarhus, Denmark.

Thomas J Corydon (TJ)

Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark.

Stefano Nebuloni (S)

RUAG Slip Rings SA, Nyon, Switzerland.

Samuel Gass (S)

RUAG Slip Rings SA, Nyon, Switzerland.

Matthias Evert (M)

Institute for Pathology, University of Regensburg, Regensburg, Germany.

Manfred Infanger (M)

Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University Magdeburg, Magdeburg, Germany.

Daniel Grimm (D)

Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University Magdeburg, Magdeburg, Germany.
Department of Biomedicine, Aarhus University, Aarhus, Denmark, dgg@biomed.au.dk.

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Classifications MeSH