Multiple paracrine factors secreted by mesenchymal stem cells contribute to angiogenesis.
Vascul Pharmacol
; 63(1): 19-28, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-24998908
ABSTRACT
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-ß1). 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-ß1 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neovascularização Fisiológica
/
Comunicação Parácrina
/
Células-Tronco Mesenquimais
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Isquemia
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Animals
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Vascul Pharmacol
Assunto da revista:
ANGIOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article