Insulin-like growth factor 1 enhances the migratory capacity of mesenchymal stem cells

doi:10.1016/j.bbrc.2007.03.049

Biochemical and Biophysical Research Communications

Volume 356, Issue 3, 11 May 2007, Pages 780-784

https://doi.org/10.1016/j.bbrc.2007.03.049 Get rights and content

Abstract

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.

Section snippets

Materials and methods

Materials. IGF-1 was purchased from GroPep (Australia); PI3K-inhibitors (LY294002 and wortmannin), MEK-specific inhibitors (PD98095) were from Cell Signaling (Beverly, MA); anti-IGF-1 antibody was from Santa Cruz Biotechnology (Santa Cruz, CA). SDF-1 and blocking CXCR4 antibody were from R&D Systems (Minneapolis, MN).

MSC culture. Bone marrow was extruded from Lewis rat tibias and femurs using a 23-gauge needle. Cells were cultured in α-MEM supplemented with 20% FBS. After 24 h, HSCs and

Effect of IGF-1 on MSC proliferation and cell cycle

To determine the effect of IGF-1 on cell cycle, we used flow cytometry and found that 85.3% ± 5.1% of MSC were in G1 phase, 3.5% ± 2.1% in S phase (Fig. 1). IGF-1 did not alter the cell cycle distribution after 48 h exposure (87.1% ± 3.6% of MSC in G1 phase, and 4.5% ± 1.3% of MSC in S phase). Moreover, IGF-1 (0–20 ng/ml, 0–48 h) did not alter MSC proliferation as determined by BrdU assay (Fig. 2).

IGF-1 increases the expression of CXCR4

IGF-1 increased the expression of CXCR4 when compared with control as shown by real-time PCR analysis (Fig. 3

Discussion

In the present study, we demonstrated that IGF-1 increases the expression of CXCR4 and enhances SDF-1-induced MSC migration via PI-3-kinase pathway. To our knowledge, these novel findings have not been reported before.

Our finding that IGF-1 enhanced migration of MSCs was inhibited by pretreatment with blocking anti-CXCR4 antibody indicates that IGF-1 increased MSC migration is CXCR4 dependent. These findings are consistent with previous reports that CXCR4 receptors are essentially involved in

Acknowledgments

This work was supported by American Heart Association (0555331B, Y.-H. Song), National Natural Science Foundation of China (30271287, 30300421, and 30571850 to X. Yu).

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¹: These authors contributed equally to this work.

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Insulin-like growth factor 1 enhances the migratory capacity of mesenchymal stem cells

Abstract

Section snippets

Materials and methods

Effect of IGF-1 on MSC proliferation and cell cycle

IGF-1 increases the expression of CXCR4

Discussion

Acknowledgments

Blood

Cell

J. Biol. Chem.

J. Mol. Cell. Cardiol.

J. Mol Cell Cardiol.

Blood

J. Mol Cell Cardiol

J. Biol. Chem.

Blood

Blood

Blood

Blood

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Science

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Proc. Natl. Acad. Sci. USA

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Nat. Med.

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