| First Author | Wang K | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 9 | Pages | e43922 |
| PubMed ID | 22984452 | Mgi Jnum | J:192899 |
| Mgi Id | MGI:5466791 | Doi | 10.1371/journal.pone.0043922 |
| Citation | Wang K, et al. (2012) Overexpression of SDF-1alpha enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway. PLoS One 7(9):e43922 |
| abstractText | Cardiac stem cells (CSCs) can home to the infarcted area and regenerate myocardium. Stromal cell-derived factor-1alpha/C-X-C chemokine receptor type 4 (SDF-1alpha/CXCR4) axis is pivotal in inducing CSCs migration. However, the mechanisms remain unclear. This study set out to detect if SDF-1alpha promotes migration and engraftment of CSCs through the CXCR4/PI3K (phosphatidylinositol 3-kinase) pathway. In the in vitro experiment, c-kit+ cells were isolated from neonatal mouse heart fragment culture by magnetic cell sorting. Fluorescence-activated cell sorting results demonstrated that a few c-kit+ cells expressed CD45 (4.54%) and Sca-1 (2.58%), the hematopoietic stem cell marker. Conditioned culture could induce c-kit+ cells multipotent differentiation, which was confirmed by cardiac troponin I (cTn-I), alpha-smooth muscle actin (alpha-SMA), and von Willebrand factor (vWF) staining. In vitro chemotaxis assays were performed using Transwell cell chambers to detect CSCs migration. The results showed that the cardiomyocytes infected with rAAV1-SDF-1alpha-eGFP significantly increased SDF-1alpha concentration, 5-fold more in supernatant than that in the control group, and subsequently attracted more CSCs migration. This effect was diminished by administration of AMD3100 (10 microg/ml, CXCR4 antagonist) or LY294002 (20 micromol/L, PI3K inhibitor). In myocardial infarction mice, overexpression of SDF-1alpha in the infarcted area by rAAV1-SDF-1alpha-eGFP infection resulted in more CSCs retention to the infarcted myocardium, a higher percentage of proliferation, and reduced infarcted area which was attenuated by AMD3100 or ly294002 pretreatment. These results indicated that overexpression of SDF-1alpha enhanced CSCs migration in vitro and engraftment of transplanted CSCs and reduced infarcted size via CXCR4/PI3K pathway. |
