Growth Factor Therapy and Autologous Lymph Node Transfer in Lymphedema
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 gr...
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Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2011-02, Vol.123 (6), p.613-620 |
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creator | LÄHTEENVUO, Markku HONKONEN, Krista TERVALA, Tomi TAMMELA, Tuomas SUOMINEN, Erkki LÄHTEENVUO, Johanna KHOLOVA, Ivana ALITALO, Kari YLÄ-HERTTUALA, Seppo SAARISTO, Anne |
description | 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.
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.
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. |
doi_str_mv | 10.1161/circulationaha.110.965384 |
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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.
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.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/circulationaha.110.965384</identifier><identifier>PMID: 21282502</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adenoviruses, Human ; Animals ; beta-Galactosidase - genetics ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood. Blood coagulation. Reticuloendothelial system ; Cardiology. Vascular system ; Disease Models, Animal ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Genetic Therapy - methods ; Genetic Vectors ; Lymph Nodes - transplantation ; Lymphedema - pathology ; Lymphedema - surgery ; Lymphedema - therapy ; Medical sciences ; Pharmacology. Drug treatments ; Seroma - therapy ; Swine ; Vascular Endothelial Growth Factor C - genetics ; Vascular Endothelial Growth Factor D - genetics</subject><ispartof>Circulation (New York, N.Y.), 2011-02, Vol.123 (6), p.613-620</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-bdb4d5739ceed221b56b8ab7c2e0a54401f426830386bdfdef132c36284f5bbe3</citedby><cites>FETCH-LOGICAL-c463t-bdb4d5739ceed221b56b8ab7c2e0a54401f426830386bdfdef132c36284f5bbe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23865879$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21282502$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>LÄHTEENVUO, Markku</creatorcontrib><creatorcontrib>HONKONEN, Krista</creatorcontrib><creatorcontrib>TERVALA, Tomi</creatorcontrib><creatorcontrib>TAMMELA, Tuomas</creatorcontrib><creatorcontrib>SUOMINEN, Erkki</creatorcontrib><creatorcontrib>LÄHTEENVUO, Johanna</creatorcontrib><creatorcontrib>KHOLOVA, Ivana</creatorcontrib><creatorcontrib>ALITALO, Kari</creatorcontrib><creatorcontrib>YLÄ-HERTTUALA, Seppo</creatorcontrib><creatorcontrib>SAARISTO, Anne</creatorcontrib><title>Growth Factor Therapy and Autologous Lymph Node Transfer in Lymphedema</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>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.
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.
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.</description><subject>Adenoviruses, Human</subject><subject>Animals</subject><subject>beta-Galactosidase - genetics</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood. Blood coagulation. Reticuloendothelial system</subject><subject>Cardiology. Vascular system</subject><subject>Disease Models, Animal</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors</subject><subject>Lymph Nodes - transplantation</subject><subject>Lymphedema - pathology</subject><subject>Lymphedema - surgery</subject><subject>Lymphedema - therapy</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Seroma - therapy</subject><subject>Swine</subject><subject>Vascular Endothelial Growth Factor C - genetics</subject><subject>Vascular Endothelial Growth Factor D - genetics</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtLw0AUhQdRtFb_gsSFuEqdd5JlKPYBoQVJ12FesZEkU2cSpP_ekVZdXe7hO_ceDgCPCM4Q4uhFNU6NrRga24u9CBqcZZyRlF6ACWKYxpSR7BJMIIRZnBCMb8Ct9x9h5SRh1-AGI5xiBvEELJbOfg37aCHUYF1U7o0Th2Mkeh3l42Bb-25HHxXH7rCPNlabqHSi97VxUdOfZKNNJ-7AVS1ab-7Pcwp2i9dyvoqL7XI9z4tYUU6GWGpJNUtIpozRGCPJuEyFTBQ2UDBKIaop5imBJOVS19rUiGBFOE5pzaQ0ZAqeT3cPzn6Oxg9V13hl2lb0JgStUoYyQjOOApmdSOWs987U1cE1nXDHCsHqp8Vqvn6b74q8XG83-SoPGqxOLQbvw_nLKDuj_5y_tQXg6QwIr0Rbh05U4_-5EJ-lSUa-AWdeffs</recordid><startdate>20110215</startdate><enddate>20110215</enddate><creator>LÄHTEENVUO, Markku</creator><creator>HONKONEN, Krista</creator><creator>TERVALA, Tomi</creator><creator>TAMMELA, Tuomas</creator><creator>SUOMINEN, Erkki</creator><creator>LÄHTEENVUO, Johanna</creator><creator>KHOLOVA, Ivana</creator><creator>ALITALO, Kari</creator><creator>YLÄ-HERTTUALA, Seppo</creator><creator>SAARISTO, Anne</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20110215</creationdate><title>Growth Factor Therapy and Autologous Lymph Node Transfer in Lymphedema</title><author>LÄHTEENVUO, Markku ; HONKONEN, Krista ; TERVALA, Tomi ; TAMMELA, Tuomas ; SUOMINEN, Erkki ; LÄHTEENVUO, Johanna ; KHOLOVA, Ivana ; ALITALO, Kari ; YLÄ-HERTTUALA, Seppo ; SAARISTO, Anne</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-bdb4d5739ceed221b56b8ab7c2e0a54401f426830386bdfdef132c36284f5bbe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adenoviruses, Human</topic><topic>Animals</topic><topic>beta-Galactosidase - genetics</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blood. Blood coagulation. Reticuloendothelial system</topic><topic>Cardiology. Vascular system</topic><topic>Disease Models, Animal</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Genetic Therapy - methods</topic><topic>Genetic Vectors</topic><topic>Lymph Nodes - transplantation</topic><topic>Lymphedema - pathology</topic><topic>Lymphedema - surgery</topic><topic>Lymphedema - therapy</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Seroma - therapy</topic><topic>Swine</topic><topic>Vascular Endothelial Growth Factor C - genetics</topic><topic>Vascular Endothelial Growth Factor D - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LÄHTEENVUO, Markku</creatorcontrib><creatorcontrib>HONKONEN, Krista</creatorcontrib><creatorcontrib>TERVALA, Tomi</creatorcontrib><creatorcontrib>TAMMELA, Tuomas</creatorcontrib><creatorcontrib>SUOMINEN, Erkki</creatorcontrib><creatorcontrib>LÄHTEENVUO, Johanna</creatorcontrib><creatorcontrib>KHOLOVA, Ivana</creatorcontrib><creatorcontrib>ALITALO, Kari</creatorcontrib><creatorcontrib>YLÄ-HERTTUALA, Seppo</creatorcontrib><creatorcontrib>SAARISTO, Anne</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>LÄHTEENVUO, Markku</au><au>HONKONEN, Krista</au><au>TERVALA, Tomi</au><au>TAMMELA, Tuomas</au><au>SUOMINEN, Erkki</au><au>LÄHTEENVUO, Johanna</au><au>KHOLOVA, Ivana</au><au>ALITALO, Kari</au><au>YLÄ-HERTTUALA, Seppo</au><au>SAARISTO, Anne</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Growth Factor Therapy and Autologous Lymph Node Transfer in Lymphedema</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2011-02-15</date><risdate>2011</risdate><volume>123</volume><issue>6</issue><spage>613</spage><epage>620</epage><pages>613-620</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>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.
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.
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.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>21282502</pmid><doi>10.1161/circulationaha.110.965384</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adenoviruses, Human Animals beta-Galactosidase - genetics Biological and medical sciences Blood and lymphatic vessels Blood. Blood coagulation. Reticuloendothelial system Cardiology. Vascular system Disease Models, Animal Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Genetic Therapy - methods Genetic Vectors Lymph Nodes - transplantation Lymphedema - pathology Lymphedema - surgery Lymphedema - therapy Medical sciences Pharmacology. Drug treatments Seroma - therapy Swine Vascular Endothelial Growth Factor C - genetics Vascular Endothelial Growth Factor D - genetics |
title | Growth Factor Therapy and Autologous Lymph Node Transfer in Lymphedema |
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