Tissue plasminogen activator (tPA), aside from its vascular fibrinolytic action, exerts

various effects within the body, ranging fromsynaptic plasticity to control of cell fate. Here,

we observed that by activating plasminogen and matrixmetalloproteinase-9, tPA expands

murine bone marrow–derived CD452TER1192Sca-11PDGFRa1 mesenchymal stromal

cells (PaS-MSCs) in vivo through a crosstalk between PaS-MSCs and endothelial cells.

Mechanistically, tPA induces the release of Kit ligand from PaS-MSCs, which activates

c-Kit1 endothelial cells to secrete MSC growth factors: platelet-derived growth factor-BB

(PDGF-BB) and fibroblast growth factor 2 (FGF2). In synergy, FGF2 and PDGF-BB

upregulate PDGFRa expression in PaS-MSCs, which ultimately leads to PaS-MSC expansion.

These data show a novel mechanism by which the fibrinolytic system expands

PaS-MSCs through a cytokine crosstalk between niche cells

Title

Blood

Publisher

The American Society of Hematology

Publisher Country

United States of America

Publication Type

Prtinted only

Volume

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Year

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Pages

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