Adipose-derived stem cells promote lymphangiogenesis in response to VEGF-C stimulation or TGF-Β1 inhibition Journal Article
| Authors: | Yan, A.; Avraham, T.; Zampell, J. C.; Haviv, Y. S.; Weitman, E.; Mehrara, B. J. |
| Article Title: | Adipose-derived stem cells promote lymphangiogenesis in response to VEGF-C stimulation or TGF-Β1 inhibition |
| Abstract: | Aims: Recent studies have demonstrated that augmentation of lymphangiogenesis and tissue engineering hold promise as a treatment for lymphedema. The purpose of this study was to determine whether adipose-derived stem cells (ASCs) can be used in lymphatic tissue-engineering by altering the balance between pro- and anti-lymphangiogenic cytokines. Materials & methods: ASCs were harvested and cultured in media with or without recombinant VEGF-C for 48 h. ASCs were then implanted in mice using Matrigel plugs. Additional groups of animals were implanted with ASCs transfected with a dominant-negative TGF-Β1 receptor-II adenovirus with or without VEGF-C stimulation, since TGF-Β1 has been shown to have potent antilymphangiogenic effects. Lymphangiogenesis, lymphatic differentiation and cellular proliferation were assessed. Results: Stimulation of ASCs with VEGF-C in vitro significantly increased expression of VEGF-A, VEGF-C and Prox-1. ASCs stimulated with VEGF-C prior to implantation induced a significant (threefold increase) lymphangiogenic response as compared with control groups (unstimulated ASCs or empty Matrigel plugs; p < 0.01). This effect was significantly potentiated when TGF-Β1 signaling was inhibited using the dominant-negative TGF-Β1 receptor-II virus (4.5-fold increase; p < 0.01). Stimulation of ASCs with VEGF-C resulted in a marked increase in the number of donor ASCs (twofold; p < 0.01) and increased the number of proliferating cells (sevenfold; p < 0.01) surrounding the Matrigel. ASCs stimulated with VEGF-C expressed podoplanin, a lymphangiogenic cell marker, whereas unstimulated cells did not. Conclusion: Short-term stimulation of ASCs with VEGF-C results in increased expression of VEGF-A, VEGF-C and Prox-1 in vitro and is associated with a marked increase lymphangiogenic response after in vivo implantation. This lymphangiogenic response is significantly potentiated by blocking TGF-Β1 function. Furthermore, stimulation of ASCs with VEGF-C markedly increases cellular proliferation and cellular survival after in vivo implantation and stimulated cells express podoplanin, a lymphangiogenic cell marker. © 2011 Future Medicine Ltd. |
| Keywords: | signal transduction; vasculotropin receptor 3; controlled study; protein expression; nonhuman; protein localization; cell proliferation; mouse; animals; mice; cell survival; cells, cultured; cd34 antigen; transforming growth factor beta; animal experiment; in vivo study; in vitro study; mice, inbred c57bl; mice, transgenic; vasculotropin c; lymphangiogenesis; vascular endothelial growth factor c; podoplanin; membrane glycoproteins; vasculotropin a; endoglin; transforming growth factor beta1; cell migration; stem cells; genes, reporter; tissue engineering; cd45 antigen; cd31 antigen; hek293 cells; 5' nucleotidase; adipocytes; vegf-c; beta1 integrin; adipose derived stem cell; adipose-derived stem cells; antilymphangiogenic; ataxin 1; tgf-? |
| Journal Title: | Future Oncology |
| Volume: | 7 |
| Issue: | 12 |
| ISSN: | 1479-6694 |
| Publisher: | Future Medicine |
| Date Published: | 2011-12-01 |
| Start Page: | 1457 |
| End Page: | 1473 |
| Language: | English |
| DOI: | 10.2217/fon.11.121 |
| PROVIDER: | scopus |
| PUBMED: | 22112321 |
| PMCID: | PMC3263831 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 January 2012" - "Source: Scopus" |
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