Insulin-like growth factor 1 enhances the migratory capacity of mesenchymal stem cells.
Mesenchymal stem cells (MSCs) are attractive candidates for cell based therapies. However, the mechanisms responsible for stem cell migration and homing after transplantation remain unknown. It has been shown that insulin-like growth factor-1 (IGF-1) induces proliferation and migration of some cell types, but its effects on stem cells have not been investigated. We isolated and cultured MSC from rat bone marrow, and found that IGF-1 increased the expression levels of the chemokine receptor CXCR4 (receptor for stromal cell-derived factor-1, SDF-1). Moreover, IGF-1 markedly increased the migratory response of MSC to SDF-1. The IGF-1-induced increase in MSC migration in response to SDF-1 was attenuated by PI3 kinase inhibitor (LY294002 and wortmannin) but not by mitogen-activated protein/ERK kinase inhibitor PD98059. Our data indicate that IGF-1 increases MSC migratory responses via CXCR4 chemokine receptor signaling which is PI3/Akt dependent. These findings provide a new paradigm for biological effects of IGF-1 on MSC and have implications for the development of novel stem cell therapeutic strategies.
Li
Yangxin
Y
Laboratory of Heart Failure and Stem Cell, Texas Heart Institute, Houston, TX 77030, USA. Yangxin_li@yahoo.com
Yu
XiYong
X
Lin
ShuGuang
S
Li
XiaoHong
X
Zhang
Saidan
S
Song
Yao-Hua
YH
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology; D002867:Chromones / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D011917:Rats, Inbred Lew; D019718:Receptors, CXCR4 / Q000502:physiology; D015398:Signal Transduction; D000077191:Wortmannin
D000730:Androstadienes; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D002867:Chromones; C486264:Cxcr4 protein, rat; D005419:Flavonoids; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019718:Receptors, CXCR4; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007334:Insulin-Like Growth Factor I; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin