Improvement of the Survival of Human Autologous Fat Transplantation by Using VEGF-Transfected Adipose-Derived Stem Cells

The efficacy of autologous fat transplantation is reduced by fat absorption and fibrosis due to fat necrosis. Enhanced transplant neovascularization early after transplantation may reduce these outcomes. The authors asked whether cell and concomitant gene therapy using adipose-derived stem cells tra...

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Veröffentlicht in:Plastic and reconstructive surgery (1963) 2009-11, Vol.124 (5), p.1437-1446
Hauptverfasser: Lu, Feng, Li, Jie, Gao, JianHua, Ogawa, Rei, Ou, Chunquan, Yang, Bo, Fu, Bingchuan
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container_end_page 1446
container_issue 5
container_start_page 1437
container_title Plastic and reconstructive surgery (1963)
container_volume 124
creator Lu, Feng
Li, Jie
Gao, JianHua
Ogawa, Rei
Ou, Chunquan
Yang, Bo
Fu, Bingchuan
description The efficacy of autologous fat transplantation is reduced by fat absorption and fibrosis due to fat necrosis. Enhanced transplant neovascularization early after transplantation may reduce these outcomes. The authors asked whether cell and concomitant gene therapy using adipose-derived stem cells transduced with vascular endothelial growth factor (VEGF) improves fat transplant neovascularization and survival. Human adipose-derived stem cells were expanded ex vivo for three passages, labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiI), and transduced with VEGF or left untransduced. Human fat tissues were then mixed with the DiI-labeled VEGF-transduced adipose-derived stem cells, the DiI-labeled adipose-derived stem cells, the known vascularization-promoting agent insulin, or medium alone, and 18 nude mice were injected subcutaneously with all four preparations, with each of the four designated spots receiving one of these four mixtures in a random fashion. Six months later, transplanted tissue volume and histology were evaluated and neovascularization was quantified by counting the capillaries. Control transplant survival was 27.1 +/- 8.2 percent, but mixture with the VEGF-transduced and VEGF-untransduced stem cells significantly increased transplant survival (74.1 +/- 12.6 percent and 60.1 +/- 17.6 percent, respectively). Insulin was less effective (37.7 +/- 6.9 percent). Histological analysis revealed both types of transplants consisted predominantly of adipose tissue, unlike the control transplants, and had significantly less fat necrosis and fibrosis. The VEGF-transduced, adipose-derived stem cell-treated transplants had significantly higher capillary density than the other transplants and bore DiI-double-positive and CD31-double-positive cells (i.e., adipose-derived stem cell-derived endothelial cells). Adipose-derived stem cells together with VEGF transduction can enhance the survival and quality of transplanted fat tissues.
doi_str_mv 10.1097/PRS.0b013e3181babbb6
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Enhanced transplant neovascularization early after transplantation may reduce these outcomes. The authors asked whether cell and concomitant gene therapy using adipose-derived stem cells transduced with vascular endothelial growth factor (VEGF) improves fat transplant neovascularization and survival. Human adipose-derived stem cells were expanded ex vivo for three passages, labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiI), and transduced with VEGF or left untransduced. Human fat tissues were then mixed with the DiI-labeled VEGF-transduced adipose-derived stem cells, the DiI-labeled adipose-derived stem cells, the known vascularization-promoting agent insulin, or medium alone, and 18 nude mice were injected subcutaneously with all four preparations, with each of the four designated spots receiving one of these four mixtures in a random fashion. Six months later, transplanted tissue volume and histology were evaluated and neovascularization was quantified by counting the capillaries. Control transplant survival was 27.1 +/- 8.2 percent, but mixture with the VEGF-transduced and VEGF-untransduced stem cells significantly increased transplant survival (74.1 +/- 12.6 percent and 60.1 +/- 17.6 percent, respectively). Insulin was less effective (37.7 +/- 6.9 percent). Histological analysis revealed both types of transplants consisted predominantly of adipose tissue, unlike the control transplants, and had significantly less fat necrosis and fibrosis. The VEGF-transduced, adipose-derived stem cell-treated transplants had significantly higher capillary density than the other transplants and bore DiI-double-positive and CD31-double-positive cells (i.e., adipose-derived stem cell-derived endothelial cells). Adipose-derived stem cells together with VEGF transduction can enhance the survival and quality of transplanted fat tissues.</description><identifier>ISSN: 0032-1052</identifier><identifier>EISSN: 1529-4242</identifier><identifier>DOI: 10.1097/PRS.0b013e3181babbb6</identifier><identifier>PMID: 20009828</identifier><language>eng</language><publisher>Hagerstown, MD: American Society of Plastic Surgeons</publisher><subject>Adenoviridae ; Adipocytes - transplantation ; Adipose Tissue - cytology ; Adipose Tissue - transplantation ; Animals ; Biological and medical sciences ; Gene Expression Regulation, Viral ; Graft Survival ; Humans ; Medical sciences ; Mice ; Mice, Nude ; Models, Animal ; Neovascularization, Physiologic - genetics ; Stem Cell Transplantation - methods ; Surgery (general aspects). Transplantations, organ and tissue grafts. 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Enhanced transplant neovascularization early after transplantation may reduce these outcomes. The authors asked whether cell and concomitant gene therapy using adipose-derived stem cells transduced with vascular endothelial growth factor (VEGF) improves fat transplant neovascularization and survival. Human adipose-derived stem cells were expanded ex vivo for three passages, labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiI), and transduced with VEGF or left untransduced. Human fat tissues were then mixed with the DiI-labeled VEGF-transduced adipose-derived stem cells, the DiI-labeled adipose-derived stem cells, the known vascularization-promoting agent insulin, or medium alone, and 18 nude mice were injected subcutaneously with all four preparations, with each of the four designated spots receiving one of these four mixtures in a random fashion. Six months later, transplanted tissue volume and histology were evaluated and neovascularization was quantified by counting the capillaries. Control transplant survival was 27.1 +/- 8.2 percent, but mixture with the VEGF-transduced and VEGF-untransduced stem cells significantly increased transplant survival (74.1 +/- 12.6 percent and 60.1 +/- 17.6 percent, respectively). Insulin was less effective (37.7 +/- 6.9 percent). Histological analysis revealed both types of transplants consisted predominantly of adipose tissue, unlike the control transplants, and had significantly less fat necrosis and fibrosis. The VEGF-transduced, adipose-derived stem cell-treated transplants had significantly higher capillary density than the other transplants and bore DiI-double-positive and CD31-double-positive cells (i.e., adipose-derived stem cell-derived endothelial cells). Adipose-derived stem cells together with VEGF transduction can enhance the survival and quality of transplanted fat tissues.</description><subject>Adenoviridae</subject><subject>Adipocytes - transplantation</subject><subject>Adipose Tissue - cytology</subject><subject>Adipose Tissue - transplantation</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Gene Expression Regulation, Viral</subject><subject>Graft Survival</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Models, Animal</subject><subject>Neovascularization, Physiologic - genetics</subject><subject>Stem Cell Transplantation - methods</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Transduction, Genetic</subject><subject>Transfection</subject><subject>Transgenes</subject><subject>Transplantation, Autologous</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><issn>0032-1052</issn><issn>1529-4242</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkF9v0zAUxS0EYmXwDRDyC-Ipw3_iOH6syrpNmgSiG6-W41yvAScuttOxb4_LypB4so79u-f6HITeUnJGiZIfv3zdnJGOUA6ctrQzXdc1z9CCCqaqmtXsOVoQwllFiWAn6FVK3wmhkjfiJTphhBDVsnaBfl2Nuxj2MMKUcXA4bwFv5rgf9sYf9OU8mgkv5xx8uAtzwmuT8U00U9p5M2WThzDh7gHfpmG6w9_OL9bVn1cHNkOPl_2wCwmqTxCHfdGbDCNegffpNXrhjE_w5nieotv1-c3qsrr-fHG1Wl5Xtq6lqnjNTeOoqFtjWd9S2TWSGdJax61QTBDrGqsk9KJvhbU9SNY4SbhquXWWAT9FHx59S8yfM6SsxyHZ8gMzQcmjJa-pkoI2hawfSRtDShGc3sVhNPFBU6IPletSuf6_8jL27rhg7kbon4b-dlyA90fAJGu8K_XYIf3jGGWClpxP---DzxDTDz_fQ9RbMD5vdXEjjeB1VXwVpUVVhyvFfwN73Jwb</recordid><startdate>20091101</startdate><enddate>20091101</enddate><creator>Lu, Feng</creator><creator>Li, Jie</creator><creator>Gao, JianHua</creator><creator>Ogawa, Rei</creator><creator>Ou, Chunquan</creator><creator>Yang, Bo</creator><creator>Fu, Bingchuan</creator><general>American Society of Plastic Surgeons</general><general>Lippincott Williams &amp; 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>20091101</creationdate><title>Improvement of the Survival of Human Autologous Fat Transplantation by Using VEGF-Transfected Adipose-Derived Stem Cells</title><author>Lu, Feng ; Li, Jie ; Gao, JianHua ; Ogawa, Rei ; Ou, Chunquan ; Yang, Bo ; Fu, Bingchuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4479-343a6f1548ac2d817b672a08cf3c59250cf6c97ed5d85ccde726f703983cfc2e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adenoviridae</topic><topic>Adipocytes - transplantation</topic><topic>Adipose Tissue - cytology</topic><topic>Adipose Tissue - transplantation</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Gene Expression Regulation, Viral</topic><topic>Graft Survival</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Models, Animal</topic><topic>Neovascularization, Physiologic - genetics</topic><topic>Stem Cell Transplantation - methods</topic><topic>Surgery (general aspects). 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Graft diseases</topic><topic>Transduction, Genetic</topic><topic>Transfection</topic><topic>Transgenes</topic><topic>Transplantation, Autologous</topic><topic>Vascular Endothelial Growth Factor A - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, Feng</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Gao, JianHua</creatorcontrib><creatorcontrib>Ogawa, Rei</creatorcontrib><creatorcontrib>Ou, Chunquan</creatorcontrib><creatorcontrib>Yang, Bo</creatorcontrib><creatorcontrib>Fu, Bingchuan</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>Plastic and reconstructive surgery (1963)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Feng</au><au>Li, Jie</au><au>Gao, JianHua</au><au>Ogawa, Rei</au><au>Ou, Chunquan</au><au>Yang, Bo</au><au>Fu, Bingchuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improvement of the Survival of Human Autologous Fat Transplantation by Using VEGF-Transfected Adipose-Derived Stem Cells</atitle><jtitle>Plastic and reconstructive surgery (1963)</jtitle><addtitle>Plast Reconstr Surg</addtitle><date>2009-11-01</date><risdate>2009</risdate><volume>124</volume><issue>5</issue><spage>1437</spage><epage>1446</epage><pages>1437-1446</pages><issn>0032-1052</issn><eissn>1529-4242</eissn><abstract>The efficacy of autologous fat transplantation is reduced by fat absorption and fibrosis due to fat necrosis. Enhanced transplant neovascularization early after transplantation may reduce these outcomes. The authors asked whether cell and concomitant gene therapy using adipose-derived stem cells transduced with vascular endothelial growth factor (VEGF) improves fat transplant neovascularization and survival. Human adipose-derived stem cells were expanded ex vivo for three passages, labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiI), and transduced with VEGF or left untransduced. Human fat tissues were then mixed with the DiI-labeled VEGF-transduced adipose-derived stem cells, the DiI-labeled adipose-derived stem cells, the known vascularization-promoting agent insulin, or medium alone, and 18 nude mice were injected subcutaneously with all four preparations, with each of the four designated spots receiving one of these four mixtures in a random fashion. Six months later, transplanted tissue volume and histology were evaluated and neovascularization was quantified by counting the capillaries. Control transplant survival was 27.1 +/- 8.2 percent, but mixture with the VEGF-transduced and VEGF-untransduced stem cells significantly increased transplant survival (74.1 +/- 12.6 percent and 60.1 +/- 17.6 percent, respectively). Insulin was less effective (37.7 +/- 6.9 percent). Histological analysis revealed both types of transplants consisted predominantly of adipose tissue, unlike the control transplants, and had significantly less fat necrosis and fibrosis. The VEGF-transduced, adipose-derived stem cell-treated transplants had significantly higher capillary density than the other transplants and bore DiI-double-positive and CD31-double-positive cells (i.e., adipose-derived stem cell-derived endothelial cells). Adipose-derived stem cells together with VEGF transduction can enhance the survival and quality of transplanted fat tissues.</abstract><cop>Hagerstown, MD</cop><pub>American Society of Plastic Surgeons</pub><pmid>20009828</pmid><doi>10.1097/PRS.0b013e3181babbb6</doi><tpages>10</tpages></addata></record>
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ispartof Plastic and reconstructive surgery (1963), 2009-11, Vol.124 (5), p.1437-1446
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subjects Adenoviridae
Adipocytes - transplantation
Adipose Tissue - cytology
Adipose Tissue - transplantation
Animals
Biological and medical sciences
Gene Expression Regulation, Viral
Graft Survival
Humans
Medical sciences
Mice
Mice, Nude
Models, Animal
Neovascularization, Physiologic - genetics
Stem Cell Transplantation - methods
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Transduction, Genetic
Transfection
Transgenes
Transplantation, Autologous
Vascular Endothelial Growth Factor A - genetics
title Improvement of the Survival of Human Autologous Fat Transplantation by Using VEGF-Transfected Adipose-Derived Stem Cells
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