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Extracellular Matrix Synthesis and Remodeling by Mesenchymal Stromal Cells Is Context-Sensitive

Matrix remodeling could be an important mode of action of multipotent mesenchymal
stromal cells (MSC) in extracellular matrix (ECM) disease, but knowledge is limited in this respect.
As MSC are well-known to adapt their behavior to their environment, we aimed to investigate
if their mode of action would change in response to healthy versus pathologically altered ECM.
Human MSC-derived ECM was produced under different culture conditions, including standard
culture, culture on Matrigel-coated dishes, and stimulation with the pro-fibrotic transforming growth
factor-1 (TGF1). The MSC-ECM was decellularized, characterized by histochemistry, and used
as MSC culture substrate reflecting different ECM conditions. MSC were cultured on the different
ECM substrates or in control conditions for 2 days. Culture on ECM increased the presence of surface
molecules with ECM receptor function in the MSC, demonstrating an interaction between MSC
and ECM. In MSC cultured on Matrigel-ECM and TGF1-ECM, which displayed a fibrosis-like
morphology, gene expression of collagens and decorin, as well as total matrix metalloproteinase
(MMP) activity in the supernatant were decreased as compared with control conditions. These
results demonstrated that MSC adapt to their ECM environment, which may include pathological
adaptations that could compromise therapeutic efficacy.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89053
Date16 January 2024
CreatorsBurk, Janina, Sassmann, Anna, Kasper, Cornelia, Nimptsch, Ariane, Schubert, Susanna
PublisherMDPI
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text
Rightsinfo:eu-repo/semantics/openAccess
Relation1758

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