Multiple paracrine factors secreted by mesenchymal stem cells contribute to angiogenesis

Hyuk Min Kwon, Sung Mo Hur, Keon Young Park, Chun Ki Kim, Yong Man Kim, Hyun Soo Kim, Ha Cheol Shin, Moo Ho Won, Kwon Soo Ha, Young-Guen Kwon, Dong Heon Lee, Young Myeong Kim

Research output: Contribution to journalArticle

54 Citations (Scopus)

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-β1). 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-β1 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.

Original languageEnglish
Pages (from-to)19-28
Number of pages10
JournalVascular Pharmacology
Volume63
Issue number1
DOIs
Publication statusPublished - 2014 Oct 1

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Mesenchymal Stromal Cells
Chemokine CCL2
Vascular Endothelial Growth Factor A
Transforming Growth Factor beta1
Interleukin-6
Hepatocyte Growth Factor
Antibodies
Stem Cell Transplantation
Therapeutic Uses
Hindlimb
Conditioned Culture Medium
Neutralizing Antibodies
Human Activities
Intercellular Signaling Peptides and Proteins
Therapeutics
Ischemia
Endothelial Cells
Cytokines
Injections

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Medicine
  • Pharmacology

Cite this

Kwon, H. M., Hur, S. M., Park, K. Y., Kim, C. K., Kim, Y. M., Kim, H. S., ... Kim, Y. M. (2014). Multiple paracrine factors secreted by mesenchymal stem cells contribute to angiogenesis. Vascular Pharmacology, 63(1), 19-28. https://doi.org/10.1016/j.vph.2014.06.004
Kwon, Hyuk Min ; Hur, Sung Mo ; Park, Keon Young ; Kim, Chun Ki ; Kim, Yong Man ; Kim, Hyun Soo ; Shin, Ha Cheol ; Won, Moo Ho ; Ha, Kwon Soo ; Kwon, Young-Guen ; Lee, Dong Heon ; Kim, Young Myeong. / Multiple paracrine factors secreted by mesenchymal stem cells contribute to angiogenesis. In: Vascular Pharmacology. 2014 ; Vol. 63, No. 1. pp. 19-28.
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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-β1). 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-β1 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.",
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Kwon, HM, Hur, SM, Park, KY, Kim, CK, Kim, YM, Kim, HS, Shin, HC, Won, MH, Ha, KS, Kwon, Y-G, Lee, DH & Kim, YM 2014, 'Multiple paracrine factors secreted by mesenchymal stem cells contribute to angiogenesis', Vascular Pharmacology, vol. 63, no. 1, pp. 19-28. https://doi.org/10.1016/j.vph.2014.06.004

Multiple paracrine factors secreted by mesenchymal stem cells contribute to angiogenesis. / Kwon, Hyuk Min; Hur, Sung Mo; Park, Keon Young; Kim, Chun Ki; Kim, Yong Man; Kim, Hyun Soo; Shin, Ha Cheol; Won, Moo Ho; Ha, Kwon Soo; Kwon, Young-Guen; Lee, Dong Heon; Kim, Young Myeong.

In: Vascular Pharmacology, Vol. 63, No. 1, 01.10.2014, p. 19-28.

Research output: Contribution to journalArticle

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AU - Kwon, Hyuk Min

AU - Hur, Sung Mo

AU - Park, Keon Young

AU - Kim, Chun Ki

AU - Kim, Yong Man

AU - Kim, Hyun Soo

AU - Shin, Ha Cheol

AU - Won, Moo Ho

AU - Ha, Kwon Soo

AU - Kwon, Young-Guen

AU - Lee, Dong Heon

AU - Kim, Young Myeong

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Y1 - 2014/10/1

N2 - 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-β1). 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-β1 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.

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