Leukemia inhibitory factor-transfected embryonic fibroblasts and vascular endothelial growth factor successfully improve the skin substitute wound healing by increasing angiogenesis and matrix production
Background and objective : The combined application of cytokines on embryonic fibroblasts and dermal substitute were studied for optimal skin defect coverage. The mechanism of combined treatment of leukemia inhibitory factor (LIF)-transfected embryonic fibroblasts and vascular endothelial growth fac...
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creator | Akita, Sadanori Daian, Takahiro Ishihara, Hiroshi Fujii, Tohru Akino, Kozo |
description | Background and objective
: The combined application of cytokines on embryonic fibroblasts and dermal substitute were studied for optimal skin defect coverage. The mechanism of combined treatment of leukemia inhibitory factor (LIF)-transfected embryonic fibroblasts and vascular endothelial growth factor (VEGF) were elucidated and subsequently the in vivo applications of both were tested in an artificial dermal substitute.
Methods
: Mouse embryonic fibroblast cells, BALB-3T3, were stably transfected with mouse full-length LIF cDNA and added to various doses of VEGF for detection of signaling interaction. LIF-transfected cells and VEGF treatment were tested with pig-tendon derived collagen dermal substitute in the backs of BALB/c male mice up to for 14 days.
Results
: LIF-transfected cells as well as vector-transfected fibroblasts significantly proliferated by 1, 10, or 100
ng VEGF on days 3 and 5. Erk mitogen-activated protein (MAP) kinase phosphorylation was observed from 1 to 30
min in LIF-transfected and 10
ng of VEFG, and 1 to 60
min in LIF-transfected and 100
ng VEFG treatments. The cellular fibronectin levels also increased in LIF-transfected cells with 10 and 100
ng VEGF additions. In in vivo analyses, LIF-transfected embryonic fibroblasts with 50
μg of VEGF markedly enhanced collagen I expression and CD34 angiogenic marker on days 7 and 14.
Conclusion
: LIF transfection and VEGF treatment enhanced phosphorylated-Erk-MAP kinase in vitro. In vivo study revealed that the combined application of LIF transfection of embryonic fibroblasts with an angiogenic factor such as VEGF in the template of a dermal substitute induced greater skin collagen production and angiogenesis in the dermal substitute. |
doi_str_mv | 10.1016/j.jdermsci.2004.05.007 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_66977287</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S092318110400101X</els_id><sourcerecordid>66977287</sourcerecordid><originalsourceid>FETCH-LOGICAL-c398t-b37e6b791af4264298ba1aa81b412a3de530aa7df55c21800a3332ca111faf9e3</originalsourceid><addsrcrecordid>eNqFkcuOEzEQRS0EYkLgF0Zesetg97t3oBEDSJHYgMTOKrurk8q47cF2Z8g38lM4ShBLViXLp-5V6TB2K8VGCtm-O2wOI4Y5GtqUQtQb0WyE6J6xley7qmja4cdzthJDWRWyl_KGvYrxIIRoynp4yW5kU_d9J-SK_d7i8oAzASe3J03JhxOfwORZpAAuTmgSjhxnHU7ekeET6eC1hZgiBzfyI0SzWAgc3ejTHi2B5bvgn9L-GsTjYgzGOC3WnjjNj8EfkWeUxwdy-VfHRGlJyJ_8khP3CJbcjusMOxMQ4vkFbkd-hw4jXYpnSIF-8Zw2LiaRd6_ZiwlsxDfXuWbf7z9-u_tcbL9--nL3YVuYauhToasOW90NEqa6bOty6DVIgF7qWpZQjdhUAqAbp6YxpeyFgKqqSgNSygmmAas1e3vJzdU_F4xJzRQNWgsO_RJV2w5dV2YPa9ZeQBN8jAEn9RhohnBSUqizRnVQfzWqs0YlGpU15sXba8OiZxz_rV29ZeD9BcB855EwqByBzuBIIQtTo6f_dfwBI0C6mA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>66977287</pqid></control><display><type>article</type><title>Leukemia inhibitory factor-transfected embryonic fibroblasts and vascular endothelial growth factor successfully improve the skin substitute wound healing by increasing angiogenesis and matrix production</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Akita, Sadanori ; Daian, Takahiro ; Ishihara, Hiroshi ; Fujii, Tohru ; Akino, Kozo</creator><creatorcontrib>Akita, Sadanori ; Daian, Takahiro ; Ishihara, Hiroshi ; Fujii, Tohru ; Akino, Kozo</creatorcontrib><description>Background and objective
: The combined application of cytokines on embryonic fibroblasts and dermal substitute were studied for optimal skin defect coverage. The mechanism of combined treatment of leukemia inhibitory factor (LIF)-transfected embryonic fibroblasts and vascular endothelial growth factor (VEGF) were elucidated and subsequently the in vivo applications of both were tested in an artificial dermal substitute.
Methods
: Mouse embryonic fibroblast cells, BALB-3T3, were stably transfected with mouse full-length LIF cDNA and added to various doses of VEGF for detection of signaling interaction. LIF-transfected cells and VEGF treatment were tested with pig-tendon derived collagen dermal substitute in the backs of BALB/c male mice up to for 14 days.
Results
: LIF-transfected cells as well as vector-transfected fibroblasts significantly proliferated by 1, 10, or 100
ng VEGF on days 3 and 5. Erk mitogen-activated protein (MAP) kinase phosphorylation was observed from 1 to 30
min in LIF-transfected and 10
ng of VEFG, and 1 to 60
min in LIF-transfected and 100
ng VEFG treatments. The cellular fibronectin levels also increased in LIF-transfected cells with 10 and 100
ng VEGF additions. In in vivo analyses, LIF-transfected embryonic fibroblasts with 50
μg of VEGF markedly enhanced collagen I expression and CD34 angiogenic marker on days 7 and 14.
Conclusion
: LIF transfection and VEGF treatment enhanced phosphorylated-Erk-MAP kinase in vitro. In vivo study revealed that the combined application of LIF transfection of embryonic fibroblasts with an angiogenic factor such as VEGF in the template of a dermal substitute induced greater skin collagen production and angiogenesis in the dermal substitute.</description><identifier>ISSN: 0923-1811</identifier><identifier>EISSN: 1873-569X</identifier><identifier>DOI: 10.1016/j.jdermsci.2004.05.007</identifier><identifier>PMID: 15488701</identifier><language>eng</language><publisher>Netherlands: Elsevier Ireland Ltd</publisher><subject>3T3 Cells ; Angiogenesis ; Animals ; Antigens, CD34 - biosynthesis ; Blotting, Western ; Cell Proliferation ; Collagen - metabolism ; Cutaneous regeneration ; DNA, Complementary - metabolism ; Extracellular Matrix - metabolism ; Fibroblasts - metabolism ; Fibronectins - metabolism ; Immunohistochemistry ; Interleukin-6 - genetics ; Leukemia Inhibitory Factor ; Male ; MAP Kinase Signaling System ; Mice ; Mice, Inbred BALB C ; Mitogen-Activated Protein Kinase 1 - metabolism ; Mitogen-Activated Protein Kinase 3 - metabolism ; Neovascularization, Pathologic ; Phosphorylation ; Reverse Transcriptase Polymerase Chain Reaction ; RNA - metabolism ; Signal Transduction ; Skin - metabolism ; Time Factors ; Transfection ; Vascular Endothelial Growth Factor A - metabolism ; Wound healing</subject><ispartof>Journal of dermatological science, 2004-10, Vol.36 (1), p.11-23</ispartof><rights>2004 Japanese Society for Investigative Dermatology</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c398t-b37e6b791af4264298ba1aa81b412a3de530aa7df55c21800a3332ca111faf9e3</citedby><cites>FETCH-LOGICAL-c398t-b37e6b791af4264298ba1aa81b412a3de530aa7df55c21800a3332ca111faf9e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S092318110400101X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15488701$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Akita, Sadanori</creatorcontrib><creatorcontrib>Daian, Takahiro</creatorcontrib><creatorcontrib>Ishihara, Hiroshi</creatorcontrib><creatorcontrib>Fujii, Tohru</creatorcontrib><creatorcontrib>Akino, Kozo</creatorcontrib><title>Leukemia inhibitory factor-transfected embryonic fibroblasts and vascular endothelial growth factor successfully improve the skin substitute wound healing by increasing angiogenesis and matrix production</title><title>Journal of dermatological science</title><addtitle>J Dermatol Sci</addtitle><description>Background and objective
: The combined application of cytokines on embryonic fibroblasts and dermal substitute were studied for optimal skin defect coverage. The mechanism of combined treatment of leukemia inhibitory factor (LIF)-transfected embryonic fibroblasts and vascular endothelial growth factor (VEGF) were elucidated and subsequently the in vivo applications of both were tested in an artificial dermal substitute.
Methods
: Mouse embryonic fibroblast cells, BALB-3T3, were stably transfected with mouse full-length LIF cDNA and added to various doses of VEGF for detection of signaling interaction. LIF-transfected cells and VEGF treatment were tested with pig-tendon derived collagen dermal substitute in the backs of BALB/c male mice up to for 14 days.
Results
: LIF-transfected cells as well as vector-transfected fibroblasts significantly proliferated by 1, 10, or 100
ng VEGF on days 3 and 5. Erk mitogen-activated protein (MAP) kinase phosphorylation was observed from 1 to 30
min in LIF-transfected and 10
ng of VEFG, and 1 to 60
min in LIF-transfected and 100
ng VEFG treatments. The cellular fibronectin levels also increased in LIF-transfected cells with 10 and 100
ng VEGF additions. In in vivo analyses, LIF-transfected embryonic fibroblasts with 50
μg of VEGF markedly enhanced collagen I expression and CD34 angiogenic marker on days 7 and 14.
Conclusion
: LIF transfection and VEGF treatment enhanced phosphorylated-Erk-MAP kinase in vitro. In vivo study revealed that the combined application of LIF transfection of embryonic fibroblasts with an angiogenic factor such as VEGF in the template of a dermal substitute induced greater skin collagen production and angiogenesis in the dermal substitute.</description><subject>3T3 Cells</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Antigens, CD34 - biosynthesis</subject><subject>Blotting, Western</subject><subject>Cell Proliferation</subject><subject>Collagen - metabolism</subject><subject>Cutaneous regeneration</subject><subject>DNA, Complementary - metabolism</subject><subject>Extracellular Matrix - metabolism</subject><subject>Fibroblasts - metabolism</subject><subject>Fibronectins - metabolism</subject><subject>Immunohistochemistry</subject><subject>Interleukin-6 - genetics</subject><subject>Leukemia Inhibitory Factor</subject><subject>Male</subject><subject>MAP Kinase Signaling System</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mitogen-Activated Protein Kinase 1 - metabolism</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>Neovascularization, Pathologic</subject><subject>Phosphorylation</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA - metabolism</subject><subject>Signal Transduction</subject><subject>Skin - metabolism</subject><subject>Time Factors</subject><subject>Transfection</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>Wound healing</subject><issn>0923-1811</issn><issn>1873-569X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcuOEzEQRS0EYkLgF0Zesetg97t3oBEDSJHYgMTOKrurk8q47cF2Z8g38lM4ShBLViXLp-5V6TB2K8VGCtm-O2wOI4Y5GtqUQtQb0WyE6J6xley7qmja4cdzthJDWRWyl_KGvYrxIIRoynp4yW5kU_d9J-SK_d7i8oAzASe3J03JhxOfwORZpAAuTmgSjhxnHU7ekeET6eC1hZgiBzfyI0SzWAgc3ejTHi2B5bvgn9L-GsTjYgzGOC3WnjjNj8EfkWeUxwdy-VfHRGlJyJ_8khP3CJbcjusMOxMQ4vkFbkd-hw4jXYpnSIF-8Zw2LiaRd6_ZiwlsxDfXuWbf7z9-u_tcbL9--nL3YVuYauhToasOW90NEqa6bOty6DVIgF7qWpZQjdhUAqAbp6YxpeyFgKqqSgNSygmmAas1e3vJzdU_F4xJzRQNWgsO_RJV2w5dV2YPa9ZeQBN8jAEn9RhohnBSUqizRnVQfzWqs0YlGpU15sXba8OiZxz_rV29ZeD9BcB855EwqByBzuBIIQtTo6f_dfwBI0C6mA</recordid><startdate>200410</startdate><enddate>200410</enddate><creator>Akita, Sadanori</creator><creator>Daian, Takahiro</creator><creator>Ishihara, Hiroshi</creator><creator>Fujii, Tohru</creator><creator>Akino, Kozo</creator><general>Elsevier Ireland Ltd</general><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>200410</creationdate><title>Leukemia inhibitory factor-transfected embryonic fibroblasts and vascular endothelial growth factor successfully improve the skin substitute wound healing by increasing angiogenesis and matrix production</title><author>Akita, Sadanori ; Daian, Takahiro ; Ishihara, Hiroshi ; Fujii, Tohru ; Akino, Kozo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c398t-b37e6b791af4264298ba1aa81b412a3de530aa7df55c21800a3332ca111faf9e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>3T3 Cells</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Antigens, CD34 - biosynthesis</topic><topic>Blotting, Western</topic><topic>Cell Proliferation</topic><topic>Collagen - metabolism</topic><topic>Cutaneous regeneration</topic><topic>DNA, Complementary - metabolism</topic><topic>Extracellular Matrix - metabolism</topic><topic>Fibroblasts - metabolism</topic><topic>Fibronectins - metabolism</topic><topic>Immunohistochemistry</topic><topic>Interleukin-6 - genetics</topic><topic>Leukemia Inhibitory Factor</topic><topic>Male</topic><topic>MAP Kinase Signaling System</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mitogen-Activated Protein Kinase 1 - metabolism</topic><topic>Mitogen-Activated Protein Kinase 3 - metabolism</topic><topic>Neovascularization, Pathologic</topic><topic>Phosphorylation</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA - metabolism</topic><topic>Signal Transduction</topic><topic>Skin - metabolism</topic><topic>Time Factors</topic><topic>Transfection</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Akita, Sadanori</creatorcontrib><creatorcontrib>Daian, Takahiro</creatorcontrib><creatorcontrib>Ishihara, Hiroshi</creatorcontrib><creatorcontrib>Fujii, Tohru</creatorcontrib><creatorcontrib>Akino, Kozo</creatorcontrib><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>Journal of dermatological science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Akita, Sadanori</au><au>Daian, Takahiro</au><au>Ishihara, Hiroshi</au><au>Fujii, Tohru</au><au>Akino, Kozo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leukemia inhibitory factor-transfected embryonic fibroblasts and vascular endothelial growth factor successfully improve the skin substitute wound healing by increasing angiogenesis and matrix production</atitle><jtitle>Journal of dermatological science</jtitle><addtitle>J Dermatol Sci</addtitle><date>2004-10</date><risdate>2004</risdate><volume>36</volume><issue>1</issue><spage>11</spage><epage>23</epage><pages>11-23</pages><issn>0923-1811</issn><eissn>1873-569X</eissn><abstract>Background and objective
: The combined application of cytokines on embryonic fibroblasts and dermal substitute were studied for optimal skin defect coverage. The mechanism of combined treatment of leukemia inhibitory factor (LIF)-transfected embryonic fibroblasts and vascular endothelial growth factor (VEGF) were elucidated and subsequently the in vivo applications of both were tested in an artificial dermal substitute.
Methods
: Mouse embryonic fibroblast cells, BALB-3T3, were stably transfected with mouse full-length LIF cDNA and added to various doses of VEGF for detection of signaling interaction. LIF-transfected cells and VEGF treatment were tested with pig-tendon derived collagen dermal substitute in the backs of BALB/c male mice up to for 14 days.
Results
: LIF-transfected cells as well as vector-transfected fibroblasts significantly proliferated by 1, 10, or 100
ng VEGF on days 3 and 5. Erk mitogen-activated protein (MAP) kinase phosphorylation was observed from 1 to 30
min in LIF-transfected and 10
ng of VEFG, and 1 to 60
min in LIF-transfected and 100
ng VEFG treatments. The cellular fibronectin levels also increased in LIF-transfected cells with 10 and 100
ng VEGF additions. In in vivo analyses, LIF-transfected embryonic fibroblasts with 50
μg of VEGF markedly enhanced collagen I expression and CD34 angiogenic marker on days 7 and 14.
Conclusion
: LIF transfection and VEGF treatment enhanced phosphorylated-Erk-MAP kinase in vitro. In vivo study revealed that the combined application of LIF transfection of embryonic fibroblasts with an angiogenic factor such as VEGF in the template of a dermal substitute induced greater skin collagen production and angiogenesis in the dermal substitute.</abstract><cop>Netherlands</cop><pub>Elsevier Ireland Ltd</pub><pmid>15488701</pmid><doi>10.1016/j.jdermsci.2004.05.007</doi><tpages>13</tpages></addata></record> |
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source | MEDLINE; Elsevier ScienceDirect Journals |
subjects | 3T3 Cells Angiogenesis Animals Antigens, CD34 - biosynthesis Blotting, Western Cell Proliferation Collagen - metabolism Cutaneous regeneration DNA, Complementary - metabolism Extracellular Matrix - metabolism Fibroblasts - metabolism Fibronectins - metabolism Immunohistochemistry Interleukin-6 - genetics Leukemia Inhibitory Factor Male MAP Kinase Signaling System Mice Mice, Inbred BALB C Mitogen-Activated Protein Kinase 1 - metabolism Mitogen-Activated Protein Kinase 3 - metabolism Neovascularization, Pathologic Phosphorylation Reverse Transcriptase Polymerase Chain Reaction RNA - metabolism Signal Transduction Skin - metabolism Time Factors Transfection Vascular Endothelial Growth Factor A - metabolism Wound healing |
title | Leukemia inhibitory factor-transfected embryonic fibroblasts and vascular endothelial growth factor successfully improve the skin substitute wound healing by increasing angiogenesis and matrix production |
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