LymphedemaV1, Pmc, Corpus, bibRecord, 002989

Adipose-derived stem cells promote lymphangiogenesis in response to VEGF-C stimulation or TGF-β1 inhibition

Identifieur interne : 002989 ( Pmc/Corpus ); précédent : 002988; suivant : 002990

Adipose-derived stem cells promote lymphangiogenesis in response to VEGF-C stimulation or TGF-β1 inhibition

Auteurs : Alan Yan ; Tomer Avraham ; Jamie C. Zampell ; Yosef S. Haviv ; Evan Weitman ; Babak J. Mehrara

Source :

Future Oncology (London, England) [ 1479-6694 ] ; 2011.

RBID : PMC:3263831

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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263831

DOI: 10.2217/fon.11.121
PubMed: 22112321
PubMed Central: 3263831

Links to Exploration step

PMC:3263831

Le document en format XML

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<author><name sortKey="Yan, Alan" sort="Yan, Alan" uniqKey="Yan A" first="Alan" last="Yan">Alan Yan</name>
<affiliation><nlm:aff id="A1">The Division of Plastic & Reconstructive Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Avraham, Tomer" sort="Avraham, Tomer" uniqKey="Avraham T" first="Tomer" last="Avraham">Tomer Avraham</name>
<affiliation><nlm:aff id="A1">The Division of Plastic & Reconstructive Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zampell, Jamie C" sort="Zampell, Jamie C" uniqKey="Zampell J" first="Jamie C" last="Zampell">Jamie C. Zampell</name>
<affiliation><nlm:aff id="A1">The Division of Plastic & Reconstructive Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Haviv, Yosef S" sort="Haviv, Yosef S" uniqKey="Haviv Y" first="Yosef S" last="Haviv">Yosef S. Haviv</name>
<affiliation><nlm:aff id="A2">Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel</nlm:aff>
</affiliation>
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<author><name sortKey="Weitman, Evan" sort="Weitman, Evan" uniqKey="Weitman E" first="Evan" last="Weitman">Evan Weitman</name>
<affiliation><nlm:aff id="A1">The Division of Plastic & Reconstructive Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA</nlm:aff>
</affiliation>
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<author><name sortKey="Mehrara, Babak J" sort="Mehrara, Babak J" uniqKey="Mehrara B" first="Babak J" last="Mehrara">Babak J. Mehrara</name>
<affiliation><nlm:aff id="A1">The Division of Plastic & Reconstructive Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA</nlm:aff>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Adipose-derived stem cells promote lymphangiogenesis in response to VEGF-C stimulation or TGF-β1 inhibition</title>
<author><name sortKey="Yan, Alan" sort="Yan, Alan" uniqKey="Yan A" first="Alan" last="Yan">Alan Yan</name>
<affiliation><nlm:aff id="A1">The Division of Plastic & Reconstructive Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Avraham, Tomer" sort="Avraham, Tomer" uniqKey="Avraham T" first="Tomer" last="Avraham">Tomer Avraham</name>
<affiliation><nlm:aff id="A1">The Division of Plastic & Reconstructive Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zampell, Jamie C" sort="Zampell, Jamie C" uniqKey="Zampell J" first="Jamie C" last="Zampell">Jamie C. Zampell</name>
<affiliation><nlm:aff id="A1">The Division of Plastic & Reconstructive Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Haviv, Yosef S" sort="Haviv, Yosef S" uniqKey="Haviv Y" first="Yosef S" last="Haviv">Yosef S. Haviv</name>
<affiliation><nlm:aff id="A2">Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Weitman, Evan" sort="Weitman, Evan" uniqKey="Weitman E" first="Evan" last="Weitman">Evan Weitman</name>
<affiliation><nlm:aff id="A1">The Division of Plastic & Reconstructive Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Mehrara, Babak J" sort="Mehrara, Babak J" uniqKey="Mehrara B" first="Babak J" last="Mehrara">Babak J. Mehrara</name>
<affiliation><nlm:aff id="A1">The Division of Plastic & Reconstructive Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Future Oncology (London, England)</title>
<idno type="ISSN">1479-6694</idno>
<idno type="eISSN">1744-8301</idno>
<imprint><date when="2011">2011</date>
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Aims</title>
<p id="P1">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.</p>
</sec>
<sec sec-type="materials|methods" id="S2"><title>Materials & methods</title>
<p id="P2">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.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">Stimulation of ASCs with VEGF-C <italic>in vitro</italic>
 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.</p>
</sec>
<sec id="S4"><title>Conclusion</title>
<p id="P4">Short-term stimulation of ASCs with VEGF-C results in increased expression of VEGF-A, VEGF-C and Prox-1 <italic>in vitro</italic>
 and is associated with a marked increase lymphangiogenic response after <italic>in vivo</italic>
 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 <italic>in vivo</italic>
 implantation and stimulated cells express podoplanin, a lymphangiogenic cell marker.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article" xml:lang="en"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
  <pmc-dir>properties manuscript</pmc-dir>
  <front><journal-meta><journal-id journal-id-type="nlm-journal-id">101256629</journal-id>
<journal-id journal-id-type="pubmed-jr-id">32856</journal-id>
<journal-id journal-id-type="nlm-ta">Future Oncol</journal-id>
<journal-title-group><journal-title>Future Oncology (London, England)</journal-title>
</journal-title-group>
<issn pub-type="ppub">1479-6694</issn>
<issn pub-type="epub">1744-8301</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22112321</article-id>
<article-id pub-id-type="pmc">3263831</article-id>
<article-id pub-id-type="doi">10.2217/fon.11.121</article-id>
<article-id pub-id-type="manuscript">NIHMS347916</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Adipose-derived stem cells promote lymphangiogenesis in response to VEGF-C stimulation or TGF-β1 inhibition</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Yan</surname>
<given-names>Alan</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Avraham</surname>
<given-names>Tomer</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zampell</surname>
<given-names>Jamie C</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Haviv</surname>
<given-names>Yosef S</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Weitman</surname>
<given-names>Evan</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mehrara</surname>
<given-names>Babak J</given-names>
</name>
<xref ref-type="corresp" rid="CR1">*</xref>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
The Division of Plastic & Reconstructive Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA</aff>
<aff id="A2"><label>2</label>
Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel</aff>
<author-notes><corresp id="CR1"><label>*</label>
Author for correspondence: 1275 York Avenue, Room MRI 1005, New York, NY 10065, USA, Tel.: +1 212 639 8639, Fax: +1 212 717 3677, mehrarab@mskcc.org</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>18</day>
<month>1</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="ppub"><month>12</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>1</day>
<month>10</month>
<year>2012</year>
</pub-date>
<volume>7</volume>
<issue>12</issue>
<fpage>1457</fpage>
<lpage>1473</lpage>
<permissions><copyright-statement>© 2011 Future Medicine Ltd</copyright-statement>
<copyright-year>2011</copyright-year>
</permissions>
<abstract><sec id="S1"><title>Aims</title>
<p id="P1">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.</p>
</sec>
<sec sec-type="materials|methods" id="S2"><title>Materials & methods</title>
<p id="P2">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.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">Stimulation of ASCs with VEGF-C <italic>in vitro</italic>
 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.</p>
</sec>
<sec id="S4"><title>Conclusion</title>
<p id="P4">Short-term stimulation of ASCs with VEGF-C results in increased expression of VEGF-A, VEGF-C and Prox-1 <italic>in vitro</italic>
 and is associated with a marked increase lymphangiogenic response after <italic>in vivo</italic>
 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 <italic>in vivo</italic>
 implantation and stimulated cells express podoplanin, a lymphangiogenic cell marker.</p>
</sec>
</abstract>
<kwd-group><kwd>adipose-derived stem cells</kwd>
<kwd>antilymphangiogenic</kwd>
<kwd>lymphangiogenesis</kwd>
<kwd>TGF-β</kwd>
<kwd>tissue engineering</kwd>
<kwd>VEGF-C</kwd>
</kwd-group>
<funding-group><award-group><funding-source country="United States">National Cancer Institute  : NCI</funding-source>
<award-id>T32 CA009501-25 || CA</award-id>
</award-group>
<award-group><funding-source country="United States">National Cancer Institute  : NCI</funding-source>
<award-id>T32 CA009501-24 || CA</award-id>
</award-group>
<award-group><funding-source country="United States">National Cancer Institute  : NCI</funding-source>
<award-id>T32 CA009501-23 || CA</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
</record>

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Adipose-derived stem cells promote lymphangiogenesis in response to VEGF-C stimulation or TGF-β1 inhibition

Adipose-derived stem cells promote lymphangiogenesis in response to VEGF-C stimulation or TGF-β1 inhibition

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Abstract

Links to Exploration step

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Pour manipuler ce document sous Unix (Dilib)

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