Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium

Yao Liang Tang, Qiang Zhao, Y. Clare Zhang, Leilei Cheng, Mingya Liu, Jianhui Shi, Yin Zeng Yang, Chuizhen Pan, Junbo Ge, M. Ian Phillips

Research output: Contribution to journalArticle

340 Scopus citations

Abstract

Neovascularization induced by vascular endothelial growth factor (VEGF) represents an appealing approach for treating ischemic heart disease. However, VEGF therapy has been associated with transient therapeutic effects and potential risk for hemangioma growth. Adult mesenchymal stem cells (MSCs) derived from bone marrow are a promising source for tissue regeneration and repair. In order to achieve a safe and persistent angiogenic effect, we have explored the potential of autologous MSCs transplantation to enhance angiogenesis and cardiac function of ischemic hearts. One week after myocardial infarction induced by occlusion of left anterior descending artery, autologous MSCs expanded in vitro was administrated intramyocardially into the infarct area of the same donor rats. By 2 months, MSCs implantation significantly elevated VEGF expression levels, accompanied by increased vascular density and regional blood flow in the infarct zone. The neovascularization resulted in a decreased apoptosis of hypertrophied myocytes and markedly improved the left ventricular contractility (ejection fraction: 79.9±7.6% vs. 37.2±6.9% in control animals). Therefore, mechanisms underlying MSCs improvement of cardiac functions may involve neovascularization induced by differentiation of MSCs to endothelial cells and para-secretion of growth factors, in addition to the apoptosis reduction and previously reported cardiomyocytes regeneration. Two months after cell transplantation, there are significant improvement of left ventricular function. Hence, autologous MSCs transplantation may represent a promising therapeutic strategy free of ethical concerns and immune rejection, for neovascularization in ischemic heart diseases.

Original languageEnglish (US)
Pages (from-to)3-10
Number of pages8
JournalRegulatory Peptides
Volume117
Issue number1
DOIs
StatePublished - Jan 15 2004

Keywords

  • Marrow stromal cells
  • Myocardial infarction
  • VEGF

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cellular and Molecular Neuroscience

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    Tang, Y. L., Zhao, Q., Zhang, Y. C., Cheng, L., Liu, M., Shi, J., Yang, Y. Z., Pan, C., Ge, J., & Phillips, M. I. (2004). Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium. Regulatory Peptides, 117(1), 3-10. https://doi.org/10.1016/j.regpep.2003.09.005