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Overexpression of SDF-1? enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway.

ABSTRACT: Cardiac stem cells (CSCs) can home to the infarcted area and regenerate myocardium. Stromal cell-derived factor-1?/C-X-C chemokine receptor type 4 (SDF-1?/CXCR4) axis is pivotal in inducing CSCs migration. However, the mechanisms remain unclear. This study set out to detect if SDF-1? 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), ?-smooth muscle actin (?-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-1?-eGFP significantly increased SDF-1? 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 µg/ml, CXCR4 antagonist) or LY294002 (20 µmol/L, PI3K inhibitor). In myocardial infarction mice, overexpression of SDF-1? in the infarcted area by rAAV1-SDF-1?-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-1? enhanced CSCs migration in vitro and engraftment of transplanted CSCs and reduced infarcted size via CXCR4/PI3K pathway.

SUBMITTER: Wang K

PROVIDER: S-EPMC3439464 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Overexpression of SDF-1α enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway.

Wang Kui K Zhao Xiaohui X Kuang Chunyan C Qian Dehui D Wang Hang H Jiang Hong H Deng Mengyang M Huang Lan L

PloS one 20120911 9

Cardiac stem cells (CSCs) can home to the infarcted area and regenerate myocardium. Stromal cell-derived factor-1α/C-X-C chemokine receptor type 4 (SDF-1α/CXCR4) axis is pivotal in inducing CSCs migration. However, the mechanisms remain unclear. This study set out to detect if SDF-1α 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 magneti ...[more]

PMID: 22984452

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Dataset Information

Overexpression of SDF-1? enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway.

Publications

Overexpression of SDF-1α enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway.

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