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Extracellular Matrix Production by Mesenchymal Stromal Cells in Hydrogels Facilitates Cell Spreading and Is Inhibited by FGF‐2


Horton, Edward R; Vallmajo‐Martin, Queralt; Martin, Ivan; Snedeker, Jess G; Ehrbar, Martin; Blache, Ulrich (2020). Extracellular Matrix Production by Mesenchymal Stromal Cells in Hydrogels Facilitates Cell Spreading and Is Inhibited by FGF‐2. Advanced Healthcare Materials, 9(7):1901669.

Abstract

In native tissues, the interaction between cells and the surrounding extracellular matrix (ECM) is reciprocal, as cells not only receive signals from the ECM but also actively remodel it through secretion of cell‐derived ECM. However, very little is known about the reciprocal interaction between cells and their secreted ECM within synthetic biomaterials that mimic the ECM for use in engineering of tissues for regenerative medicine or as tissue models. Here, poly(ethylene glycol) (PEG) hydrogels with fully defined biomaterial properties are used to investigate the emerging role of cell‐derived ECM on culture outcomes. It is shown that human mesenchymal stromal cells (MSCs) secrete ECM proteins into the pericellular space early after encapsulation and that, even in the absence of material‐presented cell adhesion motifs, cell‐derived fibronectin enables cell spreading. Then, it is investigated how different culture conditions influence MSC ECM expression in hydrogels. Most strikingly, it is found by RNA sequencing that the fibroblast growth factor 2 (FGF‐2) changes ECM gene expression and, in particular, decreases the expression of structural ECM components including fibrillar collagens. In summary, this work shows that cell‐derived ECM is a guiding cue in 3D hydrogels and that FGF‐2 is a potentially important ECM regulator within bioengineered cell and tissue systems.

Abstract

In native tissues, the interaction between cells and the surrounding extracellular matrix (ECM) is reciprocal, as cells not only receive signals from the ECM but also actively remodel it through secretion of cell‐derived ECM. However, very little is known about the reciprocal interaction between cells and their secreted ECM within synthetic biomaterials that mimic the ECM for use in engineering of tissues for regenerative medicine or as tissue models. Here, poly(ethylene glycol) (PEG) hydrogels with fully defined biomaterial properties are used to investigate the emerging role of cell‐derived ECM on culture outcomes. It is shown that human mesenchymal stromal cells (MSCs) secrete ECM proteins into the pericellular space early after encapsulation and that, even in the absence of material‐presented cell adhesion motifs, cell‐derived fibronectin enables cell spreading. Then, it is investigated how different culture conditions influence MSC ECM expression in hydrogels. Most strikingly, it is found by RNA sequencing that the fibroblast growth factor 2 (FGF‐2) changes ECM gene expression and, in particular, decreases the expression of structural ECM components including fibrillar collagens. In summary, this work shows that cell‐derived ECM is a guiding cue in 3D hydrogels and that FGF‐2 is a potentially important ECM regulator within bioengineered cell and tissue systems.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Obstetrics
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Physical Sciences > Biomaterials
Physical Sciences > Biomedical Engineering
Life Sciences > Pharmaceutical Science
Uncontrolled Keywords:Computer Networks and Communications, Pharmaceutical Science, Biomaterials, Biomedical Engineering
Language:English
Date:1 April 2020
Deposited On:17 Feb 2021 07:33
Last Modified:24 Feb 2021 10:14
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:2192-2640
OA Status:Closed
Publisher DOI:https://doi.org/10.1002/adhm.201901669
PubMed ID:32129003
Project Information:
  • : FunderFP7
  • : Grant ID607868
  • : Project TitleITERM - Training scientists to develop and Image materials for Tissue Engineering and Regenerative Medicine

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