Fibrinolytic crosstalk with endothelial cells expands murine mesenchymal stromal cells

摘要

Tissue plasminogen activator (tPA), aside from its vascular fibrinolytic action, exerts various effects within the body, ranging from synaptic plasticity to control of cell fate. Here, we observed that by activating plasminogen and matrix metalloproteinase-9, tPA expands murine bone marrow-derived CD45(-) TER119(-) Sca-1(+) PDGFR alpha(+) mesenchymal stromal cells (P alpha S-MSCs) in vivo through a crosstalk between P alpha S-MSCs and endothelial cells. Mechanistically, tPA induces the release of Kit ligand from P alpha S-MSCs, which activates c-Kit(+) 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 PDGFR alpha expression in P alpha S-MSCs, which ultimately leads to P alpha S-MSC expansion. These data show a novel mechanism by which the fibrinolytic system expands P alpha S-MSCs through a cytokine crosstalk between niche cells.