Fibrinolytic crosstalk with endothelial cells expands murine mesenchymal stromal cells.
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(+)PDGFRα(+) mesenchymal stromal cells (PαS-MSCs) in vivo through a crosstalk between PαS-MSCs and endothelial cells. Mechanistically, tPA induces the release of Kit ligand from PαS-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 PDGFRα expression in PαS-MSCs, which ultimately leads to PαS-MSC expansion. These data show a novel mechanism by which the fibrinolytic system expands PαS-MSCs through a cytokine crosstalk between niche cells.
Division of Stem Cell Dynamics.
Douaa
D
Dhahri
Division of Stem Cell Dynamics.
Kaori
K
Sato-Kusubata
Division of Stem Cell Dynamics.
Makiko
M
Ohki-Koizumi
Division of Stem Cell Dynamics, Division of Stem Cell Regulation, and.
Chiemi
C
Nishida
Division of Stem Cell Regulation, and.
Yoshihiko
Y
Tashiro
Division of Stem Cell Regulation, and.
Shinya
S
Munakata
Division of Stem Cell Regulation, and.
Hiroshi
H
Shimazu
Division of Stem Cell Dynamics.
Yousef
Y
Salama
Division of Stem Cell Dynamics.
Salita
S
Eiamboonsert
Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science at the University of Tokyo, Tokyo, Japan; and.
Hiromitsu
H
Nakauchi
Division of Stem Cell Dynamics, Division of Stem Cell Regulation, and Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science at the University of Tokyo, Tokyo, Japan; and Center for Genome and Regenerative Medicine and.
Koichi
K
Hattori
Division of Stem Cell Dynamics, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science at the University of Tokyo, Tokyo, Japan; and Center for Genome and Regenerative Medicine and.
Beate
B
Heissig
D000818:Animals; D000067696:Ataxin-1 / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005342:Fibrinolysis / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D010958:Plasminogen / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D019089:Stem Cell Factor / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D000067696:Ataxin-1; D036341:Intercellular Signaling Peptides and Proteins; D019089:Stem Cell Factor; D010958:Plasminogen; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017493:Leukocyte Common Antigens; D010959:Tissue Plasminogen Activator; D020780:Matrix Metalloproteinase 9