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Title: VEGF improves survival of mesenchymal stem cells in infarcted hearts

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, p16{sup INK}, p21 and p19{sup 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.

Authors:
 [1]; ; ;  [2]; ;  [3];  [2];  [4];  [1];  [5]
  1. Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA (United States)
  2. Department of Medicine, University of California, San Francisco, San Francisco, CA (United States)
  3. Division of Cardiology, University of California, San Francisco, San Francisco, CA (United States)
  4. (United States)
  5. (United States), E-mail: hua.su@ucsf.edu
Publication Date:
OSTI Identifier:
21217105
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 376; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2008.09.003; PII: S0006-291X(08)01741-5; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BONE MARROW; CELL CYCLE; CELL PROLIFERATION; GROWTH FACTORS; MONOCLINIC LATTICES; MYOCARDIAL INFARCTION; MYOCARDIUM; STEM CELLS; STRESSES

Citation Formats

Pons, Jennifer, Huang Yu, Arakawa-Hoyt, Janice, Washko, Daniel, Takagawa, Junya, Ye, Jianqin, Grossman, William, Division of Cardiology, University of California, San Francisco, San Francisco, CA, Su Hua, and Department of Anesthesia and Perioperative, University of California, San Francisco, 1001 Potrero Avenue, Room 3C-38, San Francisco, CA 94110. VEGF improves survival of mesenchymal stem cells in infarcted hearts. United States: N. p., 2008. Web. doi:10.1016/j.bbrc.2008.09.003.
Pons, Jennifer, Huang Yu, Arakawa-Hoyt, Janice, Washko, Daniel, Takagawa, Junya, Ye, Jianqin, Grossman, William, Division of Cardiology, University of California, San Francisco, San Francisco, CA, Su Hua, & Department of Anesthesia and Perioperative, University of California, San Francisco, 1001 Potrero Avenue, Room 3C-38, San Francisco, CA 94110. VEGF improves survival of mesenchymal stem cells in infarcted hearts. United States. doi:10.1016/j.bbrc.2008.09.003.
Pons, Jennifer, Huang Yu, Arakawa-Hoyt, Janice, Washko, Daniel, Takagawa, Junya, Ye, Jianqin, Grossman, William, Division of Cardiology, University of California, San Francisco, San Francisco, CA, Su Hua, and Department of Anesthesia and Perioperative, University of California, San Francisco, 1001 Potrero Avenue, Room 3C-38, San Francisco, CA 94110. Fri . "VEGF improves survival of mesenchymal stem cells in infarcted hearts". United States. doi:10.1016/j.bbrc.2008.09.003.
@article{osti_21217105,
title = {VEGF improves survival of mesenchymal stem cells in infarcted hearts},
author = {Pons, Jennifer and Huang Yu and Arakawa-Hoyt, Janice and Washko, Daniel and Takagawa, Junya and Ye, Jianqin and Grossman, William and Division of Cardiology, University of California, San Francisco, San Francisco, CA and Su Hua and Department of Anesthesia and Perioperative, University of California, San Francisco, 1001 Potrero Avenue, Room 3C-38, San Francisco, CA 94110},
abstractNote = {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, p16{sup INK}, p21 and p19{sup 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.},
doi = {10.1016/j.bbrc.2008.09.003},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 2,
volume = 376,
place = {United States},
year = {2008},
month = {11}
}