Human umbilical cord-mesenchymal stem cells promote extracellular matrix remodeling in microglia

Lombardo, MT, Gabrielli, M, Julien-Marsollier, F, Faivre, V, Le Charpentier, T, Bokobza, C, D’Aliberti, D, Pelizzi, N, Halimi, C, Spinelli, S, Van Steenwinckel, J, Verderio, EAM ORCID: https://orcid.org/0000-0001-9153-8997, Gressens, P, Piazza, R and Verderio, C, 2024. Human umbilical cord-mesenchymal stem cells promote extracellular matrix remodeling in microglia. Cells, 13 (19): 1665. ISSN 2073-4409

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Abstract

Human mesenchymal stem cells modulate the immune response and are good candidates for cell therapy in neuroinflammatory brain disorders affecting both adult and premature infants. Recent evidence indicates that through their secretome, mesenchymal stem cells direct microglia, brain-resident immune cells, toward pro-regenerative functions, but the mechanisms underlying microglial phenotypic transition are still under investigation. Using an in vitro coculture approach combined with transcriptomic analysis, we identified the extracellular matrix as the most relevant pathway altered by the human mesenchymal stem cell secretome in the response of microglia to inflammatory cytokines. We confirmed extracellular matrix remodeling in microglia exposed to the mesenchymal stem cell secretome via immunofluorescence analysis of the matrix component fibronectin and the extracellular crosslinking enzyme transglutaminase-2. Furthermore, an analysis of hallmark microglial functions revealed that changes in the extracellular matrix enhance ruffle formation by microglia and cell motility. These findings point to extracellular matrix changes, associated plasma membrane remodeling, and enhanced microglial migration as novel mechanisms by which mesenchymal stem cells contribute to the pro-regenerative microglial transition.

Item Type:	Journal article
Publication Title:	Cells
Creators:	Lombardo, M.T., Gabrielli, M., Julien-Marsollier, F., Faivre, V., Le Charpentier, T., Bokobza, C., D’Aliberti, D., Pelizzi, N., Halimi, C., Spinelli, S., Van Steenwinckel, J., Verderio, E.A.M., Gressens, P., Piazza, R. and Verderio, C.
Publisher:	MDPI AG
Date:	October 2024
Volume:	13
Number:	19
ISSN:	2073-4409
Identifiers:	Number Type 10.3390/cells13191665 DOI 2309382 Other
Rights:	© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Divisions:	Schools > School of Science and Technology
Record created by:	Melissa Cornwell
Date Added:	06 Jan 2025 11:03
Last Modified:	06 Jan 2025 11:03
URI:	https://irep.ntu.ac.uk/id/eprint/52768

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