Overexpression of SDF-1α enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway.
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 migrat...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3439464?pdf=render |
| _version_ | 1819089456658907136 |
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| author | Kui Wang Xiaohui Zhao Chunyan Kuang Dehui Qian Hang Wang Hong Jiang Mengyang Deng Lan Huang |
| author_facet | Kui Wang Xiaohui Zhao Chunyan Kuang Dehui Qian Hang Wang Hong Jiang Mengyang Deng Lan Huang |
| author_sort | Kui Wang |
| collection | DOAJ |
| description | 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 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), α-smooth muscle actin (α-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-1α-eGFP significantly increased SDF-1α 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-1α in the infarcted area by rAAV1-SDF-1α-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-1α enhanced CSCs migration in vitro and engraftment of transplanted CSCs and reduced infarcted size via CXCR4/PI3K pathway. |
| first_indexed | 2024-12-21T22:08:14Z |
| format | Article |
| id | doaj.art-44206a8cb35c4b97b69f6867679666ac |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T22:08:14Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-44206a8cb35c4b97b69f6867679666ac2022-12-21T18:48:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4392210.1371/journal.pone.0043922Overexpression of SDF-1α enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway.Kui WangXiaohui ZhaoChunyan KuangDehui QianHang WangHong JiangMengyang DengLan HuangCardiac 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 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), α-smooth muscle actin (α-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-1α-eGFP significantly increased SDF-1α 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-1α in the infarcted area by rAAV1-SDF-1α-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-1α enhanced CSCs migration in vitro and engraftment of transplanted CSCs and reduced infarcted size via CXCR4/PI3K pathway.http://europepmc.org/articles/PMC3439464?pdf=render |
| spellingShingle | Kui Wang Xiaohui Zhao Chunyan Kuang Dehui Qian Hang Wang Hong Jiang Mengyang Deng Lan Huang Overexpression of SDF-1α enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway. PLoS ONE |
| title | Overexpression of SDF-1α enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway. |
| title_full | Overexpression of SDF-1α enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway. |
| title_fullStr | Overexpression of SDF-1α enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway. |
| title_full_unstemmed | Overexpression of SDF-1α enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway. |
| title_short | Overexpression of SDF-1α enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via CXCR4/PI3K pathway. |
| title_sort | overexpression of sdf 1α enhanced migration and engraftment of cardiac stem cells and reduced infarcted size via cxcr4 pi3k pathway |
| url | http://europepmc.org/articles/PMC3439464?pdf=render |
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