Human Umbilical Cord-Mesenchymal Stem Cells Promote Extracellular Matrix Remodeling in Microglia

被引：2

作者：

Lombardo, Marta Tiffany ^{[1
,2
]}

Gabrielli, Martina ^{[1
]}

Julien-Marsollier, Florence ^{[3
]}

Faivre, Valerie ^{[3
]}

Le Charpentier, Tifenn ^{[3
]}

Bokobza, Cindy ^{[3
]}

D'Aliberti, Deborah ^{[4
]}

Pelizzi, Nicola ^{[5
]}

Halimi, Camilla ^{[1
]}

Spinelli, Silvia ^{[4
]}

Van Steenwinckel, Juliette ^{[3
]}

Verderio, Elisabetta A. M. ^{[6
,7
]}

Gressens, Pierre ^{[3
]}

Piazza, Rocco ^{[4
]}

Verderio, Claudia ^{[1
]}

机构：

[1] Natl Res Council Italy, Inst Neurosci, Via Raoul Follereau 3, I-20854 Vedano Al Lambro, Italy

[2] Univ Milano Bicocca, Sch Med & Surg, Piazza Ateneo Nuovo 1, I-20126 Milan, Italy

[3] Univ Paris Cite, Inserm, NeuroDiderot, F-75019 Paris, France

[4] Univ Milano Bicocca, Dept Med & Surg, I-20900 Monza, Italy

[5] Chiesi Farmaceut SpA, CARE Franchise, I-43122 Parma, Italy

[6] Nottingham Trent Univ, Sch Sci & Technol, Nottingham NG11 8NS, England

[7] Univ Bologna, Dept Biol Sci BIGEA, Via Francesco Selmi 3, I-40126 Bologna, Italy

来源：

CELLS | 2024年 / 13卷 / 19期

关键词：

human umbilical cord mesenchymal stem cells; microglia; neuroinflammation; extracellular matrix; migration; ACTIVATION; RAMIFICATION; PHENOTYPE; RELEASE;

D O I：

10.3390/cells13191665

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：20

共 88 条

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