Growth Factor Therapy and Autologous Lymph Node Transfer in Lymphedema
Identifieur interne : 005454 ( Main/Exploration ); précédent : 005453; suivant : 005455Growth Factor Therapy and Autologous Lymph Node Transfer in Lymphedema
Auteurs : Markku L Hteenvuo [Finlande] ; Krista Honkonen [Finlande] ; Tomi Tervala [Turquie] ; Tuomas Tammela [Finlande] ; Erkki Suominen [Turquie] ; Johanna L Hteenvuo [Finlande] ; Ivana Kholova [Finlande] ; Kari Alitalo [Finlande] ; Seppo Yl Herttuala [Finlande] ; Anne Saaristo [Turquie, Finlande]Source :
- Circulation : (New York, N.Y.) [ 0009-7322 ] ; 2011.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Background-Lymphedema after surgery, infection, or radiation therapy is a common and often incurable problem. Application of lymphangiogenic growth factors has been shown to induce lymphangiogenesis and to reduce tissue edema. The therapeutic effect of autologous lymph node transfer combined with adenoviral growth factor expression was evaluated in a newly established porcine model of limb lymphedema. Methods and Results-The lymphatic vasculature was destroyed within a 3-cm radius around an inguinal lymph node. Lymph node grafts and adenovirally (Ad) delivered vascular endothelial growth factor (VEGF)-C (n=5) or VEGF-D (n=9) were used to reconstruct the lymphatic network in the inguinal area; AdLacZ (β-galactosidase; n=5) served as a control. Both growth factors induced robust growth of new lymphatic vessels in the defect area, and postoperative lymphatic drainage was significantly improved in the VEGF-C/D-treated pigs compared with controls. The structure of the transferred lymph nodes was best preserved in the VEGF-C-treated pigs. Interestingly, VEGF-D transiently increased accumulation of seroma fluid in the operated inguinal region postoperatively, whereas VEGF-C did not have this side effect. Conclusions-These results show that growth factor gene therapy coupled with lymph node transfer can be used to repair damaged lymphatic networks in a large animal model and provide a basis for future clinical trials of the treatment of lymphedema.
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Virtanen Institute for Molecular Sciences, University of Eastern Finland</s1><s2>Kuopio</s2><s3>FIN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Finlande</country><wicri:noRegion>Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Honkonen, Krista" sort="Honkonen, Krista" uniqKey="Honkonen K" first="Krista" last="Honkonen">Krista Honkonen</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland</s1><s2>Kuopio</s2><s3>FIN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Finlande</country><wicri:noRegion>Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Tervala, Tomi" sort="Tervala, Tomi" uniqKey="Tervala T" first="Tomi" last="Tervala">Tomi Tervala</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Plastic Surgery, Turku University Central Hospital</s1><s3>TUR</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Turquie</country><wicri:noRegion>Department of Plastic Surgery, Turku University Central Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Tammela, Tuomas" sort="Tammela, Tuomas" uniqKey="Tammela T" first="Tuomas" last="Tammela">Tuomas Tammela</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Molecular/Cancer Biology Laboratory, Department of Pathology, Haartman Institute and Institute for Molecular Medicine, Biomedicum Helsinki, University of Helsinki</s1><s2>Helsinki</s2><s3>FIN</s3><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Finlande</country><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation></author><author><name sortKey="Suominen, Erkki" sort="Suominen, Erkki" uniqKey="Suominen E" first="Erkki" last="Suominen">Erkki Suominen</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Plastic Surgery, Turku University Central Hospital</s1><s3>TUR</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Turquie</country><wicri:noRegion>Department of Plastic Surgery, Turku University Central Hospital</wicri:noRegion></affiliation></author><author><name sortKey="L Hteenvuo, Johanna" sort="L Hteenvuo, Johanna" uniqKey="L Hteenvuo J" first="Johanna" last="L Hteenvuo">Johanna L Hteenvuo</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland</s1><s2>Kuopio</s2><s3>FIN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Finlande</country><wicri:noRegion>Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Kholova, Ivana" sort="Kholova, Ivana" uniqKey="Kholova I" first="Ivana" last="Kholova">Ivana Kholova</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland</s1><s2>Kuopio</s2><s3>FIN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Finlande</country><wicri:noRegion>Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Molecular/Cancer Biology Laboratory, Department of Pathology, Haartman Institute and Institute for Molecular Medicine, Biomedicum Helsinki, University of Helsinki</s1><s2>Helsinki</s2><s3>FIN</s3><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Finlande</country><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation></author><author><name sortKey="Yl Herttuala, Seppo" sort="Yl Herttuala, Seppo" uniqKey="Yl Herttuala S" first="Seppo" last="Yl Herttuala">Seppo Yl Herttuala</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland</s1><s2>Kuopio</s2><s3>FIN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Finlande</country><wicri:noRegion>Kuopio</wicri:noRegion></affiliation></author><author><name sortKey="Saaristo, Anne" sort="Saaristo, Anne" uniqKey="Saaristo A" first="Anne" last="Saaristo">Anne Saaristo</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Plastic Surgery, Turku University Central Hospital</s1><s3>TUR</s3><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Turquie</country><wicri:noRegion>Department of Plastic Surgery, Turku University Central Hospital</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Molecular/Cancer Biology Laboratory, Department of Pathology, Haartman Institute and Institute for Molecular Medicine, Biomedicum Helsinki, University of Helsinki</s1><s2>Helsinki</s2><s3>FIN</s3><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Finlande</country><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation></author></analytic><series><title level="j" type="main">Circulation : (New York, N.Y.)</title><title level="j" type="abbreviated">Circulation : (N. Y. N.Y.)</title><idno type="ISSN">0009-7322</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Circulation : (New York, N.Y.)</title><title level="j" type="abbreviated">Circulation : (N. Y. N.Y.)</title><idno type="ISSN">0009-7322</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Autologous system</term><term>Cardiovascular disease</term><term>Growth factor</term><term>Lymph node</term><term>Lymphatic system</term><term>Lymphedema</term><term>Treatment</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Lymphoedème</term><term>Pathologie de l'appareil circulatoire</term><term>Facteur croissance</term><term>Traitement</term><term>Système autologue</term><term>Ganglion lymphatique</term><term>Système lymphatique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background-Lymphedema after surgery, infection, or radiation therapy is a common and often incurable problem. Application of lymphangiogenic growth factors has been shown to induce lymphangiogenesis and to reduce tissue edema. The therapeutic effect of autologous lymph node transfer combined with adenoviral growth factor expression was evaluated in a newly established porcine model of limb lymphedema. Methods and Results-The lymphatic vasculature was destroyed within a 3-cm radius around an inguinal lymph node. Lymph node grafts and adenovirally (Ad) delivered vascular endothelial growth factor (VEGF)-C (n=5) or VEGF-D (n=9) were used to reconstruct the lymphatic network in the inguinal area; AdLacZ (β-galactosidase; n=5) served as a control. Both growth factors induced robust growth of new lymphatic vessels in the defect area, and postoperative lymphatic drainage was significantly improved in the VEGF-C/D-treated pigs compared with controls. The structure of the transferred lymph nodes was best preserved in the VEGF-C-treated pigs. Interestingly, VEGF-D transiently increased accumulation of seroma fluid in the operated inguinal region postoperatively, whereas VEGF-C did not have this side effect. Conclusions-These results show that growth factor gene therapy coupled with lymph node transfer can be used to repair damaged lymphatic networks in a large animal model and provide a basis for future clinical trials of the treatment of lymphedema.</div></front></TEI><affiliations><list><country><li>Finlande</li><li>Turquie</li></country><region><li>Uusimaa</li></region><settlement><li>Helsinki</li></settlement><orgName><li>Université d'Helsinki</li></orgName></list><tree><country name="Finlande"><noRegion><name sortKey="L Hteenvuo, Markku" sort="L Hteenvuo, Markku" uniqKey="L Hteenvuo M" first="Markku" last="L Hteenvuo">Markku L Hteenvuo</name></noRegion><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><name sortKey="Honkonen, Krista" sort="Honkonen, Krista" uniqKey="Honkonen K" first="Krista" last="Honkonen">Krista Honkonen</name><name sortKey="Kholova, Ivana" sort="Kholova, Ivana" uniqKey="Kholova I" first="Ivana" last="Kholova">Ivana Kholova</name><name sortKey="L Hteenvuo, Johanna" sort="L Hteenvuo, Johanna" uniqKey="L Hteenvuo J" first="Johanna" last="L Hteenvuo">Johanna L Hteenvuo</name><name sortKey="Saaristo, Anne" sort="Saaristo, Anne" uniqKey="Saaristo A" first="Anne" last="Saaristo">Anne Saaristo</name><name sortKey="Tammela, Tuomas" sort="Tammela, Tuomas" uniqKey="Tammela T" first="Tuomas" last="Tammela">Tuomas Tammela</name><name sortKey="Yl Herttuala, Seppo" sort="Yl Herttuala, Seppo" uniqKey="Yl Herttuala S" first="Seppo" last="Yl Herttuala">Seppo Yl Herttuala</name></country><country name="Turquie"><noRegion><name sortKey="Tervala, Tomi" sort="Tervala, Tomi" uniqKey="Tervala T" first="Tomi" last="Tervala">Tomi Tervala</name></noRegion><name sortKey="Saaristo, Anne" sort="Saaristo, Anne" uniqKey="Saaristo A" first="Anne" last="Saaristo">Anne Saaristo</name><name sortKey="Suominen, Erkki" sort="Suominen, Erkki" uniqKey="Suominen E" first="Erkki" last="Suominen">Erkki Suominen</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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