VEGF improves survival of mesenchymal stem cells in infarcted hearts |
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Authors: | Pons Jennifer Huang Yu Arakawa-Hoyt Janice Washko Daniel Takagawa Junya Ye Jianqin Grossman William Su Hua |
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Affiliation: | a Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA b Department of Medicine, University of California, San Francisco, San Francisco, CA, USA c Division of Cardiology, University of California, San Francisco, San Francisco, CA, USA d Department of Anesthesia and Perioperative, University of California, San Francisco, 1001 Potrero Avenue, Room 3C-38, San Francisco, CA 94110, USA |
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Abstract: | Bone marrow-derived mesenchymal stem cells (MSC) are a promising source for cell-based treatment of myocardial infarction (MI), but existing strategies are restricted by low cell survival and engraftment. We examined whether vascular endothelial growth factor (VEGF) improve MSC viability in infracted hearts. We found long-term culture increased MSC-cellular stress: expressing more cell cycle inhibitors, p16INK, p21 and p19ARF. VEGF treatment reduced cellular stress, increased pro-survival factors, phosphorylated-Akt and Bcl-xL expression and cell proliferation. Co-injection of MSCs with VEGF to MI hearts increased cell engraftment and resulted in better improvement of cardiac function than that injected with MSCs or VEGF alone. In conclusion, VEGF protects MSCs from culture-induce cellular stress and improves their viability in ischemic myocardium, which results in improvements of their therapeutic effect for the treatment of MI. |
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Keywords: | MSC Cellular stress VEGF Myocardial infarction Cell engraftment |
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