VEGF improves survival of mesenchymal stem cells in infarcted hearts.
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 infarcted hearts. We found long-term culture increased MSC-cellular stress: expressing more cell cycle inhibitors, p16(INK), p21 and p19(ARF). 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.
Pons
Jennifer
J
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Huang
Yu
Y
Arakawa-Hoyt
Janice
J
Washko
Daniel
D
Takagawa
Junya
J
Ye
Jianqin
J
Grossman
William
W
Su
Hua
H
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection; D049452:Green Fluorescent Proteins / Q000235:genetics; D006321:Heart / Q000503:physiopathology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000628:therapy; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D042461:Vascular Endothelial Growth Factor A; D049452:Green Fluorescent Proteins