期刊
VASCULAR PHARMACOLOGY
卷 63, 期 1, 页码 19-28出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.vph.2014.06.004
关键词
Mesenchymal stem cell; Angiogenesis; Paracrine factor; HUVEC
资金
- National Research Foundation of Korea (NRF) - Korea government (MSIP) [NRF-2011-0028790]
- National Research Foundation of Korea [22A20130012425, 2011-0028790] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The therapeutic effects of stem cell transplantation in ischemic disease are mediated by the production of paracrine bioactive factors. However, the bioactive factors secreted by human mesenchymal stem cells (hMSCs) and their angiogenic activity are not clearly identified or determined. We here found that hMSC-derived conditioned media (hMSC-CdM) stimulated in vitro angiogenic activity of endothelial cells and contained significant levels of various growth factors and cytokines, such as vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), and transforming growth factor-beta1 (TGF-beta 1). The angiogenic activity of hMSC-CdM was significantly inhibited by pretreatment with neutralizing antibodies against VEGF, MCP-1, and IL-6, but not against TGF-beta 1 and HGF. A mixture of those inhibitory antibodies blocked CdM-mediated activation of angiogenic signals, as well as inhibited CdM-mediated in vivo angiogenesis. Moreover, local injection of CdM increased angiogenesis and promoted blood flow in mice with hindlimb ischemia, and these effects were inhibited by co-treatment with these inhibitory antibodies. These results indicate that hMSC-CdM represents a promising cell-free therapeutic strategy for neovascularization in ischemic diseases. These results suggest the combination of VEGF, MCP-1, and IL-6 as a commercial application for therapeutic angiogenesis. (C) 2014 Elsevier Inc. All rights reserved.
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