The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use
Identifieur interne : 000724 ( Istex/Corpus ); précédent : 000723; suivant : 000725The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use
Auteurs : Heiko Sorg ; Yves Harder ; Christian Krueger ; Kerstin Reimers ; Peter M. VogtSource :
- Medicinal Research Reviews [ 0198-6325 ] ; 2013-05.
English descriptors
- Teeft :
- Acad, Anemic patients, Angiogenesis, Angiogenic, Angiogenic response, Antiapoptotic, Apoptosis, Apoptotic cell death, Arteriolar dilatation, Biochem biophys, Biol, Biol chem, Blood cell production, Blood vessels, Body weight, Bone marrow, Brine, Broblasts, Buemi, Capillary perfusion, Cell death, Cerami, Chronic wounds, Clin, Closure, Contaldo, Current research, Cytokine, Dermatol, Diabetic mice, Dysfunction, Endothelial, Endothelial cells, Endothelial nitric oxide synthase, Enos, Epidermal, Epor, Erbayraktar, Erythropoiesis, Erythropoietin, Erythropoietin production, Erythropoietin receptor, Flap, Flap survival, Follicle, Galeano, Gassmann, Ghezzi, Granulation, Granulation tissue, Growth factor, Hair follicles, Hannover, Healing, Healing capacity, Hematocrit, Hematocrit increase, Hypoxia, Hypoxic conditions, Inducible, Inducible nitric oxide synthase, Inos, International units, Ischemia, Ischemic, Jelkmann, Keratinocytes, Macrophage, Masuda, Matrix, Medicinal, Medicinal research reviews, Menger, Microvascular, Mrna, Nagao, Natl, Neovascularization, Nephrol, Nephrol dial transplant, Nitric, Nitric oxide, Nonhealing wounds, Nonhematopoietic, Nonhematopoietic effects, Pathway, Perfusion, Physiol, Pivotal role, Plast, Plast reconstr surg, Plastic surgery, Pleiotropic, Pleiotropic effects, Pleiotropic functions, Proc, Proc natl acad, Random perfusion, Receptor, Recombinant, Reconstr, Reconstructive, Reconstructive surgery, Regeneration, Renal, Research reviews, Rhuepo, Sasaki, Skin regeneration, Skin wound healing, Skin wounds, Sorg, Surg, Synthase, Systemic, Tissue protection, Tissue survival, Vegf, Wound closure, Wound healing, Wound repair.
Abstract
Erythropoietin (EPO) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties. More recent data show that EPO is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems, in particular the skin. This review highlights the mechanisms of EPO in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications. There is clear evidence that EPO effectively influences all wound‐healing phases in a dose‐dependent manner. This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound. The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide (NO) synthase with a consecutive rapid supply of NO as well as an increased content of vascular endothelial growth factor (VEGF) in the wound. The improved understanding of the functions and regulatory mechanisms of EPO in the context of wound‐healing problems and ischemia/reperfusion injury, especially during flap surgery, may lead to new considerations of this growth hormone for its regular clinical application in patients.
Url:
DOI: 10.1002/med.21259
Links to Exploration step
ISTEX:457A3A1071180D46F61F16ECA4FCA3B09DCCA7CALe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use</title><author><name sortKey="Sorg, Heiko" sort="Sorg, Heiko" uniqKey="Sorg H" first="Heiko" last="Sorg">Heiko Sorg</name><affiliation><mods:affiliation>Department of Plastic, Hand‐ and Reconstructive Surgery, Hannover Medical School, 30625, Hannover, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: sorg.heiko@mh-hannover.de</mods:affiliation></affiliation></author><author><name sortKey="Harder, Yves" sort="Harder, Yves" uniqKey="Harder Y" first="Yves" last="Harder">Yves Harder</name><affiliation><mods:affiliation>Department of Plastic Surgery and Handsurgery, Klinikum rechts der Isar, Technische Universität, München, 81675 Munich, Germany</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: sorg.heiko@mh-hannover.de</mods:affiliation></affiliation></author><author><name sortKey="Krueger, Christian" sort="Krueger, Christian" uniqKey="Krueger C" first="Christian" last="Krueger">Christian Krueger</name><affiliation><mods:affiliation>Department for Trauma Surgery and Orthopedics, Regio Klinikum Pinneberg, 25421 Pinneberg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Reimers, Kerstin" sort="Reimers, Kerstin" uniqKey="Reimers K" first="Kerstin" last="Reimers">Kerstin Reimers</name><affiliation><mods:affiliation>Department of Plastic, Hand‐ and Reconstructive Surgery, Hannover Medical School, 30625, Hannover, Germany</mods:affiliation></affiliation></author><author><name sortKey="Vogt, Peter M" sort="Vogt, Peter M" uniqKey="Vogt P" first="Peter M." last="Vogt">Peter M. 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Rev.</title><idno type="ISSN">0198-6325</idno><idno type="eISSN">1098-1128</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><date type="published" when="2013-05">2013-05</date><biblScope unit="volume">33</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="637">637</biblScope><biblScope unit="page" to="664">664</biblScope></imprint><idno type="ISSN">0198-6325</idno></series><idno type="istex">457A3A1071180D46F61F16ECA4FCA3B09DCCA7CA</idno><idno type="DOI">10.1002/med.21259</idno><idno type="ArticleID">MED21259</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0198-6325</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Acad</term><term>Anemic patients</term><term>Angiogenesis</term><term>Angiogenic</term><term>Angiogenic response</term><term>Antiapoptotic</term><term>Apoptosis</term><term>Apoptotic cell death</term><term>Arteriolar dilatation</term><term>Biochem biophys</term><term>Biol</term><term>Biol chem</term><term>Blood cell production</term><term>Blood vessels</term><term>Body weight</term><term>Bone marrow</term><term>Brine</term><term>Broblasts</term><term>Buemi</term><term>Capillary perfusion</term><term>Cell death</term><term>Cerami</term><term>Chronic wounds</term><term>Clin</term><term>Closure</term><term>Contaldo</term><term>Current research</term><term>Cytokine</term><term>Dermatol</term><term>Diabetic mice</term><term>Dysfunction</term><term>Endothelial</term><term>Endothelial cells</term><term>Endothelial nitric oxide synthase</term><term>Enos</term><term>Epidermal</term><term>Epor</term><term>Erbayraktar</term><term>Erythropoiesis</term><term>Erythropoietin</term><term>Erythropoietin production</term><term>Erythropoietin receptor</term><term>Flap</term><term>Flap survival</term><term>Follicle</term><term>Galeano</term><term>Gassmann</term><term>Ghezzi</term><term>Granulation</term><term>Granulation tissue</term><term>Growth factor</term><term>Hair follicles</term><term>Hannover</term><term>Healing</term><term>Healing capacity</term><term>Hematocrit</term><term>Hematocrit increase</term><term>Hypoxia</term><term>Hypoxic conditions</term><term>Inducible</term><term>Inducible nitric oxide synthase</term><term>Inos</term><term>International units</term><term>Ischemia</term><term>Ischemic</term><term>Jelkmann</term><term>Keratinocytes</term><term>Macrophage</term><term>Masuda</term><term>Matrix</term><term>Medicinal</term><term>Medicinal research reviews</term><term>Menger</term><term>Microvascular</term><term>Mrna</term><term>Nagao</term><term>Natl</term><term>Neovascularization</term><term>Nephrol</term><term>Nephrol dial transplant</term><term>Nitric</term><term>Nitric oxide</term><term>Nonhealing wounds</term><term>Nonhematopoietic</term><term>Nonhematopoietic effects</term><term>Pathway</term><term>Perfusion</term><term>Physiol</term><term>Pivotal role</term><term>Plast</term><term>Plast reconstr surg</term><term>Plastic surgery</term><term>Pleiotropic</term><term>Pleiotropic effects</term><term>Pleiotropic functions</term><term>Proc</term><term>Proc natl acad</term><term>Random perfusion</term><term>Receptor</term><term>Recombinant</term><term>Reconstr</term><term>Reconstructive</term><term>Reconstructive surgery</term><term>Regeneration</term><term>Renal</term><term>Research reviews</term><term>Rhuepo</term><term>Sasaki</term><term>Skin regeneration</term><term>Skin wound healing</term><term>Skin wounds</term><term>Sorg</term><term>Surg</term><term>Synthase</term><term>Systemic</term><term>Tissue protection</term><term>Tissue survival</term><term>Vegf</term><term>Wound closure</term><term>Wound healing</term><term>Wound repair</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Erythropoietin (EPO) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties. More recent data show that EPO is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems, in particular the skin. This review highlights the mechanisms of EPO in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications. There is clear evidence that EPO effectively influences all wound‐healing phases in a dose‐dependent manner. This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound. The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide (NO) synthase with a consecutive rapid supply of NO as well as an increased content of vascular endothelial growth factor (VEGF) in the wound. The improved understanding of the functions and regulatory mechanisms of EPO in the context of wound‐healing problems and ischemia/reperfusion injury, especially during flap surgery, may lead to new considerations of this growth hormone for its regular clinical application in patients.</div></front></TEI><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>erythropoietin</json:string><json:string>wound healing</json:string><json:string>receptor</json:string><json:string>skin wound healing</json:string><json:string>ischemia</json:string><json:string>recombinant</json:string><json:string>ischemic</json:string><json:string>inos</json:string><json:string>sorg</json:string><json:string>medicinal research reviews</json:string><json:string>flap</json:string><json:string>vegf</json:string><json:string>rhuepo</json:string><json:string>nonhematopoietic</json:string><json:string>surg</json:string><json:string>cytokine</json:string><json:string>flap 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sorg.heiko@mh-hannover.de</json:string></affiliations></json:item><json:item><name>Yves Harder</name><affiliations><json:string>Department of Plastic Surgery and Handsurgery, Klinikum rechts der Isar, Technische Universität, München, 81675 Munich, Germany</json:string><json:string>E-mail: sorg.heiko@mh-hannover.de</json:string></affiliations></json:item><json:item><name>Christian Krueger</name><affiliations><json:string>Department for Trauma Surgery and Orthopedics, Regio Klinikum Pinneberg, 25421 Pinneberg, Germany</json:string></affiliations></json:item><json:item><name>Kerstin Reimers</name><affiliations><json:string>Department of Plastic, Hand‐ and Reconstructive Surgery, Hannover Medical School, 30625, Hannover, Germany</json:string></affiliations></json:item><json:item><name>Peter M. Vogt</name><affiliations><json:string>Department of Plastic, Hand‐ and Reconstructive Surgery, Hannover Medical School, 30625, Hannover, Germany</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>anti‐inflammation</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>dosage</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>EPO</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>microcirculation</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>VEGF</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>skin</value></json:item></subject><articleId><json:string>MED21259</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>reviewArticle</json:string></originalGenre><abstract>Erythropoietin (EPO) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties. More recent data show that EPO is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems, in particular the skin. This review highlights the mechanisms of EPO in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications. There is clear evidence that EPO effectively influences all wound‐healing phases in a dose‐dependent manner. This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound. The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide (NO) synthase with a consecutive rapid supply of NO as well as an increased content of vascular endothelial growth factor (VEGF) in the wound. The improved understanding of the functions and regulatory mechanisms of EPO in the context of wound‐healing problems and ischemia/reperfusion injury, especially during flap surgery, may lead to new considerations of this growth hormone for its regular clinical application in patients.</abstract><qualityIndicators><score>7.328</score><pdfVersion>1.3</pdfVersion><pdfPageSize>504 x 720 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractCharCount>1319</abstractCharCount><pdfWordCount>13478</pdfWordCount><pdfCharCount>87256</pdfCharCount><pdfPageCount>28</pdfPageCount><abstractWordCount>194</abstractWordCount></qualityIndicators><title>The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use</title><genre><json:string>review-article</json:string></genre><host><title>Medicinal Research Reviews</title><language><json:string>unknown</json:string></language><doi><json:string>10.1002/(ISSN)1098-1128</json:string></doi><issn><json:string>0198-6325</json:string></issn><eissn><json:string>1098-1128</json:string></eissn><publisherId><json:string>MED</json:string></publisherId><volume>33</volume><issue>3</issue><pages><first>637</first><last>664</last><total>28</total></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Review Article</value></json:item></subject></host><categories><wos><json:string>science</json:string><json:string>pharmacology & pharmacy</json:string><json:string>chemistry, medicinal</json:string></wos><scienceMetrix><json:string>natural sciences</json:string><json:string>chemistry</json:string><json:string>medicinal & biomolecular chemistry</json:string></scienceMetrix></categories><publicationDate>2013</publicationDate><copyrightDate>2013</copyrightDate><doi><json:string>10.1002/med.21259</json:string></doi><id>457A3A1071180D46F61F16ECA4FCA3B09DCCA7CA</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/457A3A1071180D46F61F16ECA4FCA3B09DCCA7CA/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/457A3A1071180D46F61F16ECA4FCA3B09DCCA7CA/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/457A3A1071180D46F61F16ECA4FCA3B09DCCA7CA/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Blackwell Publishing Ltd</publisher><availability><p>Copyright © 2013 Wiley Periodicals, Inc.© 2012 Wiley Periodicals, Inc.</p></availability><date>2012-02-15</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use</title><author xml:id="author-1"><persName><forename type="first">Heiko</forename><surname>Sorg</surname></persName><email>sorg.heiko@mh-hannover.de</email><affiliation>Department of Plastic, Hand‐ and Reconstructive Surgery, Hannover Medical School, 30625, Hannover, Germany</affiliation></author><author xml:id="author-2"><persName><forename type="first">Yves</forename><surname>Harder</surname></persName><email>sorg.heiko@mh-hannover.de</email><affiliation>Department of Plastic Surgery and Handsurgery, Klinikum rechts der Isar, Technische Universität, München, 81675 Munich, Germany</affiliation></author><author xml:id="author-3"><persName><forename type="first">Christian</forename><surname>Krueger</surname></persName><affiliation>Department for Trauma Surgery and Orthopedics, Regio Klinikum Pinneberg, 25421 Pinneberg, Germany</affiliation></author><author xml:id="author-4"><persName><forename type="first">Kerstin</forename><surname>Reimers</surname></persName><affiliation>Department of Plastic, Hand‐ and Reconstructive Surgery, Hannover Medical School, 30625, Hannover, Germany</affiliation></author><author xml:id="author-5"><persName><forename type="first">Peter M.</forename><surname>Vogt</surname></persName><affiliation>Department of Plastic, Hand‐ and Reconstructive Surgery, Hannover Medical School, 30625, Hannover, Germany</affiliation></author></analytic><monogr><title level="j">Medicinal Research Reviews</title><title level="j" type="abbrev">Med. Res. Rev.</title><idno type="pISSN">0198-6325</idno><idno type="eISSN">1098-1128</idno><idno type="DOI">10.1002/(ISSN)1098-1128</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><date type="published" when="2013-05"></date><biblScope unit="volume">33</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="637">637</biblScope><biblScope unit="page" to="664">664</biblScope></imprint></monogr><idno type="istex">457A3A1071180D46F61F16ECA4FCA3B09DCCA7CA</idno><idno type="DOI">10.1002/med.21259</idno><idno type="ArticleID">MED21259</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2012-02-15</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Erythropoietin (EPO) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties. More recent data show that EPO is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems, in particular the skin. This review highlights the mechanisms of EPO in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications. There is clear evidence that EPO effectively influences all wound‐healing phases in a dose‐dependent manner. This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound. The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide (NO) synthase with a consecutive rapid supply of NO as well as an increased content of vascular endothelial growth factor (VEGF) in the wound. The improved understanding of the functions and regulatory mechanisms of EPO in the context of wound‐healing problems and ischemia/reperfusion injury, especially during flap surgery, may lead to new considerations of this growth hormone for its regular clinical application in patients.</p></abstract><textClass><keywords scheme="keyword"><list><head>keywords</head><item><term>anti‐inflammation</term></item><item><term>dosage</term></item><item><term>EPO</term></item><item><term>microcirculation</term></item><item><term>VEGF</term></item><item><term>skin</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article-category</head><item><term>Review Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2012-02-15">Created</change><change when="2013-05">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/457A3A1071180D46F61F16ECA4FCA3B09DCCA7CA/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en" xml:id="med21259"><header><publicationMeta level="product"><doi origin="wiley" registered="yes">10.1002/(ISSN)1098-1128</doi><issn type="print">0198-6325</issn><issn type="electronic">1098-1128</issn><idGroup><id type="product" value="MED"></id></idGroup><titleGroup><title type="main" sort="MEDICINAL RESEARCH REVIEWS">Medicinal Research Reviews</title><title type="short">Med. Res. Rev.</title></titleGroup></publicationMeta><publicationMeta level="part" position="05103"><doi>10.1002/med.2013.33.issue-3</doi><copyright ownership="publisher">Copyright © 2013 Wiley Periodicals, Inc.</copyright><numberingGroup><numbering type="journalVolume" number="33">33</numbering><numbering type="journalIssue">3</numbering></numberingGroup><coverDate startDate="2013-05">May 2013</coverDate></publicationMeta><publicationMeta level="unit" position="50" type="reviewArticle" status="forIssue"><doi origin="wiley">10.1002/med.21259</doi><idGroup><id type="unit" value="MED21259"></id></idGroup><countGroup><count type="pageTotal" number="28"></count></countGroup><titleGroup><title type="articleCategory">Review Article</title><title type="tocHeading1">Review Articles</title></titleGroup><copyright ownership="publisher">© 2012 Wiley Periodicals, Inc.</copyright><eventGroup><event type="xmlCreated" agent="Aptara" date="2012-02-15"></event><event type="publishedOnlineEarlyUnpaginated" date="2012-03-19"></event><event type="publishedOnlineFinalForm" date="2013-04-11"></event><event type="firstOnline" date="2012-03-19"></event><event type="xmlConverted" agent="Converter:WILEY_ML3G_TO_WILEY_ML3GV2 version:3.8.8" date="2014-02-02"></event><event type="xmlConverted" agent="Converter:WML3G_To_WML3G version:4.6.4 mode:FullText" date="2015-10-01"></event></eventGroup><numberingGroup><numbering type="pageFirst">637</numbering><numbering type="pageLast">664</numbering></numberingGroup><correspondenceTo><i>Correspondence to</i>: Heiko Sorg, Department of Plastic, Hand‐ and Reconstructive Surgery, Hannover Medical School, Carl‐Neuberg‐Str.1, 30625 Hannover, Germany. E‐mail: <email>sorg.heiko@mh-hannover.de</email></correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:MED.MED21259.pdf"></link></linkGroup></publicationMeta><contentMeta><titleGroup><title type="main">The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use</title><title type="shortAuthors">SORG ET AL.</title><title type="short">EPO IN SKIN WOUND HEALING AND FLAP SURVIVAL</title></titleGroup><creators><creator xml:id="med21259-cr-0001" creatorRole="author" affiliationRef="#med21259-aff-0001" corresponding="yes"><personName><givenNames>Heiko</givenNames><familyName>Sorg</familyName></personName><biographyInfo xml:id="med21259-biog-0001"><p><b>Heiko Sorg</b> <i>received his M.D. degree in 2006 and his doctorate in medicine from the University of Rostock, Germany in 2007. His postdoctorate fellowship at the Institute of Experimental Surgery in Rostock included the development of novel methods for the analysis of skin wound healing with intravital fluorescence microscopy. He is now a resident at the Department of Plastic, Hand‐ and Reconstructive Surgery at Hannover Medical School under the supervision of Peter M. Vogt. His current research focuses on the molecular mechanisms of different drugs on skin wound healing, and especially on neovascularization in the healing skin</i>.</p></biographyInfo></creator><creator xml:id="med21259-cr-0002" creatorRole="author" affiliationRef="#med21259-aff-0002" corresponding="yes"><personName><givenNames>Yves</givenNames><familyName>Harder</familyName></personName><biographyInfo xml:id="med21259-biog-0002"><p><b>Yves Harder</b> <i>completed his training in General Surgery and Plastic, Reconstructive and Aesthetic Surgery, respectively, in Davos, Chur, and Bern, Switzerland to become board‐certified general surgeon (2000) and plastic surgeon (2004). Thereafter, he spent almost 2 years at the Institute for Clinical and Experimental Research at the University of Saarland in Homburg/Saar, Germany. During this research fellowship, he investigated various noninvasive strategies to prevent critically ischemic musculocutaneous tissue from necrosis, mostly based on hyperthermia and erythropoietin. This period was followed by a clinical fellowship in Reconstructive Surgery in Johannesburg, South Africa. From 2005, he worked as a consultant surgeon at the Geneva University Hospitals, where he completed his postdoctoral lecture qualification entitled “Non‐surgical preventive strategies aiming at avoiding critical ischemia in musculocutaneous flap tissue” in 2008. Currently, PD Dr. med. Harder is working as a chief consultant and associate professor at the Department of Plastic Surgery and Handsurgery at the Klinikum rechts der Isar, Technische Universität München in Munich, Germany, combining clinical work, teaching, and research</i>.</p></biographyInfo></creator><creator xml:id="med21259-cr-0003" creatorRole="author" affiliationRef="#med21259-aff-0003"><personName><givenNames>Christian</givenNames><familyName>Krueger</familyName></personName><biographyInfo xml:id="med21259-biog-0003"><p><b>Christian Krueger</b> <i>is a resident in traumasurgery and orthopedics at the Regio Klinikum Pinneberg, Germany. He is presently doing his doctorate thesis at the Institute of Experimental Surgery at Rostock University. His research interests include changes in microcirculation during wound repair, and especially the influence of erythropoietin on the mechanisms of dermal skin regeneration</i>.</p></biographyInfo></creator><creator xml:id="med21259-cr-0004" creatorRole="author" affiliationRef="#med21259-aff-0001"><personName><givenNames>Kerstin</givenNames><familyName>Reimers</familyName></personName><biographyInfo xml:id="med21259-biog-0004"><p><b>Kerstin Reimers</b> <i>is professor for regenerative biology in plastic surgery. She received her Diploma (equivalent to M.Sc.) in Biology from Ruhr University in Bochum, Germany in 1995. Subsequently, she started Ph.D. training at the Department of Medical Microbiology and Virology at the same university where she graduated in 1999 with the thesis: Identification of protein interacting with fibroblast growth factor 3 by using the yeast two hybrid system. As a postdoc, she worked on the nuclear localization of respiratory syncytial virus protein M2‐1 at the same department for a year. She continued to work at the Pharmacological Department of Ruhr University before becoming a lab manager at the Department for Plastic, Hand‐ and Reconstructive Surgery at Hannover Medical School, Germany. Her current research focuses on the development of regenerative therapies in the field of reconstructive surgery</i>.</p></biographyInfo></creator><creator xml:id="med21259-cr-0005" creatorRole="author" affiliationRef="#med21259-aff-0001"><personName><givenNames>Peter M.</givenNames><familyName>Vogt</familyName></personName><biographyInfo xml:id="med21259-biog-0005"><p><b>Peter M. Vogt</b> <i>is Professor and Chairman of the Department of Plastic, Hand‐ and Reconstructive Surgery, Burn Center Lower Saxony at Hannover Medical School, Germany. He received his medical degree from the Medical School of Frankfurt, Germany. Afterwards he received his plastic surgical training at the universities of Lübeck, Hannover, and Bochum. During his research fellowship at the Division of Plastic Surgery, Brigham and Women´s Hospital, Boston, USA, he focused on the genetic engineering of healing. His current research focuses on the tissue engineering of skin, fat, muscles and blood vessels, regenerative therapies in the field of reconstructive surgery, and chronic wounds as well as new therapy strategies in burn injury wound care</i>.</p></biographyInfo></creator></creators><affiliationGroup><affiliation xml:id="med21259-aff-0001" countryCode="DE"><orgDiv>Department of Plastic, Hand‐ and Reconstructive Surgery</orgDiv><orgName>Hannover Medical School</orgName><address><postCode>30625</postCode><city>Hannover</city><country>Germany</country></address></affiliation><affiliation xml:id="med21259-aff-0002" countryCode="DE"><orgDiv>Department of Plastic Surgery and Handsurgery</orgDiv><orgDiv>Klinikum rechts der Isar</orgDiv><orgName>Technische Universität, München</orgName><address><city>81675 Munich</city><country>Germany</country></address></affiliation><affiliation xml:id="med21259-aff-0003" countryCode="DE"><orgDiv>Department for Trauma Surgery and Orthopedics</orgDiv><orgName>Regio Klinikum Pinneberg</orgName><address><city>25421 Pinneberg</city><country>Germany</country></address></affiliation></affiliationGroup><keywordGroup type="author"><keyword xml:id="med21259-kwd-0001">anti‐inflammation</keyword><keyword xml:id="med21259-kwd-0002">dosage</keyword><keyword xml:id="med21259-kwd-0003"><fc>EPO</fc></keyword><keyword xml:id="med21259-kwd-0004">microcirculation</keyword><keyword xml:id="med21259-kwd-0005"><fc>VEGF</fc></keyword><keyword xml:id="med21259-kwd-0006">skin</keyword></keywordGroup><abstractGroup><abstract type="main"><title type="main">Abstract</title><p>Erythropoietin (<fc>EPO</fc>) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties. More recent data show that <fc>EPO</fc> is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems, in particular the skin. This review highlights the mechanisms of <fc>EPO</fc> in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications. There is clear evidence that <fc>EPO</fc> effectively influences all wound‐healing phases in a dose‐dependent manner. This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound. The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide (<fc>NO</fc>) synthase with a consecutive rapid supply of <fc>NO</fc> as well as an increased content of vascular endothelial growth factor (<fc>VEGF</fc>) in the wound. The improved understanding of the functions and regulatory mechanisms of <fc>EPO</fc> in the context of wound‐healing problems and ischemia/reperfusion injury, especially during flap surgery, may lead to new considerations of this growth hormone for its regular clinical application in patients.</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="med21259-note-0001"><p>Both authors equally contributed to this review.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>EPO IN SKIN WOUND HEALING AND FLAP SURVIVAL</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use</title></titleInfo><name type="personal"><namePart type="given">Heiko</namePart><namePart type="family">Sorg</namePart><affiliation>Department of Plastic, Hand‐ and Reconstructive Surgery, Hannover Medical School, 30625, Hannover, Germany</affiliation><affiliation>E-mail: sorg.heiko@mh-hannover.de</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Yves</namePart><namePart type="family">Harder</namePart><affiliation>Department of Plastic Surgery and Handsurgery, Klinikum rechts der Isar, Technische Universität, München, 81675 Munich, Germany</affiliation><affiliation>E-mail: sorg.heiko@mh-hannover.de</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christian</namePart><namePart type="family">Krueger</namePart><affiliation>Department for Trauma Surgery and Orthopedics, Regio Klinikum Pinneberg, 25421 Pinneberg, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Kerstin</namePart><namePart type="family">Reimers</namePart><affiliation>Department of Plastic, Hand‐ and Reconstructive Surgery, Hannover Medical School, 30625, Hannover, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Peter M.</namePart><namePart type="family">Vogt</namePart><affiliation>Department of Plastic, Hand‐ and Reconstructive Surgery, Hannover Medical School, 30625, Hannover, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="review-article" displayLabel="reviewArticle"></genre><originInfo><publisher>Blackwell Publishing Ltd</publisher><dateIssued encoding="w3cdtf">2013-05</dateIssued><dateCreated encoding="w3cdtf">2012-02-15</dateCreated><copyrightDate encoding="w3cdtf">2013</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract>Erythropoietin (EPO) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties. More recent data show that EPO is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems, in particular the skin. This review highlights the mechanisms of EPO in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications. There is clear evidence that EPO effectively influences all wound‐healing phases in a dose‐dependent manner. This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound. The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide (NO) synthase with a consecutive rapid supply of NO as well as an increased content of vascular endothelial growth factor (VEGF) in the wound. The improved understanding of the functions and regulatory mechanisms of EPO in the context of wound‐healing problems and ischemia/reperfusion injury, especially during flap surgery, may lead to new considerations of this growth hormone for its regular clinical application in patients.</abstract><subject><genre>keywords</genre><topic>anti‐inflammation</topic><topic>dosage</topic><topic>EPO</topic><topic>microcirculation</topic><topic>VEGF</topic><topic>skin</topic></subject><relatedItem type="host"><titleInfo><title>Medicinal Research Reviews</title></titleInfo><titleInfo type="abbreviated"><title>Med. Res. 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