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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Podoplanin-expressing Cells Derived from Bone Marrow Play a Crucial Role in Postnatal Lymphatic Neovascularization</title><author><name sortKey="Lee, Ji Yoon" sort="Lee, Ji Yoon" uniqKey="Lee J" first="Ji Yoon" last="Lee">Ji Yoon Lee</name><affiliation><nlm:aff id="A1">Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA</nlm:aff></affiliation></author><author><name sortKey="Park, Changwon" sort="Park, Changwon" uniqKey="Park C" first="Changwon" last="Park">Changwon Park</name><affiliation><nlm:aff id="A1">Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA</nlm:aff></affiliation></author><author><name sortKey="Cho, Yong Pil" sort="Cho, Yong Pil" uniqKey="Cho Y" first="Yong Pil" last="Cho">Yong Pil Cho</name><affiliation><nlm:aff id="A2">Department of Vascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-2dong, Songpa-gu, Seoul 138-736, Korea</nlm:aff></affiliation></author><author><name sortKey="Lee, Eugine" sort="Lee, Eugine" uniqKey="Lee E" first="Eugine" last="Lee">Eugine Lee</name><affiliation><nlm:aff id="A1">Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA</nlm:aff></affiliation></author><author><name sortKey="Kim, Hyongbum" sort="Kim, Hyongbum" uniqKey="Kim H" first="Hyongbum" last="Kim">Hyongbum Kim</name><affiliation><nlm:aff id="A1">Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA</nlm:aff></affiliation></author><author><name sortKey="Kim, Pilhan" sort="Kim, Pilhan" uniqKey="Kim P" first="Pilhan" last="Kim">Pilhan Kim</name><affiliation><nlm:aff id="A3">Harvard Medical School and Massachusetts General Hospital, Wellman Center for Photomedicine, Boston, Massachusetts 02114, USA</nlm:aff></affiliation></author><author><name sortKey="Yun, Seok H" sort="Yun, Seok H" uniqKey="Yun S" first="Seok H." last="Yun">Seok H. Yun</name><affiliation><nlm:aff id="A3">Harvard Medical School and Massachusetts General Hospital, Wellman Center for Photomedicine, Boston, Massachusetts 02114, USA</nlm:aff></affiliation></author><author><name sortKey="Yoon, Young Sup" sort="Yoon, Young Sup" uniqKey="Yoon Y" first="Young-Sup" last="Yoon">Young-Sup Yoon</name><affiliation><nlm:aff id="A1">Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20855662</idno><idno type="pmc">2989430</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989430</idno><idno type="RBID">PMC:2989430</idno><idno type="doi">10.1161/CIRCULATIONAHA.110.941468</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">002740</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002740</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Podoplanin-expressing Cells Derived from Bone Marrow Play a Crucial Role in Postnatal Lymphatic Neovascularization</title><author><name sortKey="Lee, Ji Yoon" sort="Lee, Ji Yoon" uniqKey="Lee J" first="Ji Yoon" last="Lee">Ji Yoon Lee</name><affiliation><nlm:aff id="A1">Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA</nlm:aff></affiliation></author><author><name sortKey="Park, Changwon" sort="Park, Changwon" uniqKey="Park C" first="Changwon" last="Park">Changwon Park</name><affiliation><nlm:aff id="A1">Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA</nlm:aff></affiliation></author><author><name sortKey="Cho, Yong Pil" sort="Cho, Yong Pil" uniqKey="Cho Y" first="Yong Pil" last="Cho">Yong Pil Cho</name><affiliation><nlm:aff id="A2">Department of Vascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-2dong, Songpa-gu, Seoul 138-736, Korea</nlm:aff></affiliation></author><author><name sortKey="Lee, Eugine" sort="Lee, Eugine" uniqKey="Lee E" first="Eugine" last="Lee">Eugine Lee</name><affiliation><nlm:aff id="A1">Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA</nlm:aff></affiliation></author><author><name sortKey="Kim, Hyongbum" sort="Kim, Hyongbum" uniqKey="Kim H" first="Hyongbum" last="Kim">Hyongbum Kim</name><affiliation><nlm:aff id="A1">Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA</nlm:aff></affiliation></author><author><name sortKey="Kim, Pilhan" sort="Kim, Pilhan" uniqKey="Kim P" first="Pilhan" last="Kim">Pilhan Kim</name><affiliation><nlm:aff id="A3">Harvard Medical School and Massachusetts General Hospital, Wellman Center for Photomedicine, Boston, Massachusetts 02114, USA</nlm:aff></affiliation></author><author><name sortKey="Yun, Seok H" sort="Yun, Seok H" uniqKey="Yun S" first="Seok H." last="Yun">Seok H. Yun</name><affiliation><nlm:aff id="A3">Harvard Medical School and Massachusetts General Hospital, Wellman Center for Photomedicine, Boston, Massachusetts 02114, USA</nlm:aff></affiliation></author><author><name sortKey="Yoon, Young Sup" sort="Yoon, Young Sup" uniqKey="Yoon Y" first="Young-Sup" last="Yoon">Young-Sup Yoon</name><affiliation><nlm:aff id="A1">Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA</nlm:aff></affiliation></author></analytic><series><title level="j">Circulation</title><idno type="ISSN">0009-7322</idno><idno type="eISSN">1524-4539</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title><p id="P3">Emerging evidence has suggested a contribution of bone marrow (BM) cells to lymphatic vessel formation; however, the exact phenotype of the cells with lymphatic endothelial progenitor cell (LEPC) function has yet to be identified. Here we investigate the identity of BM-derived LEPCs and their role in lymphatic neovascularization.</p></sec><sec sec-type="methods" id="S2"><title>Methods and Results</title><p id="P4">Culture of BM-mononuclear cells (MNCs) in the presence of VEGFA, VEGFC and EGF resulted in expression of lymphatic endothelial cell (LEC) markers. Among these cells, podoplanin<sup>+</sup> cells were isolated by magnetic-labeled cell separation system (MACS) and characterized by FACS and immunocytochemistry. These podoplanin<sup>+</sup> cells highly express markers for LECs, hematopoietic lineages, and stem/progenitor cells, and upon further cultivation, generate LECs. We further confirmed that podoplanin<sup>+</sup> cells exist in small numbers in BM and peripheral blood (PB) of normal mice, but are significantly (15 fold) augmented upon lymphangiogenic stimuli such as tumor implantation. Next, to evaluate the potential of podoplanin<sup>+</sup> cells for the formation of new lymphatic vessels <italic>in vivo</italic>, we injected culture-isolated or freshly isolated BM-derived podoplanin+ cells into wound and tumor models. Immunohistochemistry demonstrated that the injected cells were incorporated into the lymphatic vasculature, displayed LEC phenotypes, and increased lymphatic vascular density in tissues, suggesting lymphvasculogenesis. Podoplanin<sup>+</sup> cells also expressed high levels of lymphangiogenic cytokines and increased proliferation of LECs during co-culture, suggesting a lymphangiogenic or paracrine role.</p></sec><sec id="S3"><title>Conclusions</title><p id="P5">Our results provide compelling evidence that BM-derived podoplanin<sup>+</sup> cells, a previously unrecognized cell type, function as LEPCs and participate in postnatal lymphatic neovascularization through both lymphvasculogenesis and lymphangiogenesis.</p></sec></div></front></TEI><pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0147763</journal-id><journal-id journal-id-type="pubmed-jr-id">2979</journal-id><journal-id journal-id-type="nlm-ta">Circulation</journal-id><journal-title>Circulation</journal-title><issn pub-type="ppub">0009-7322</issn><issn pub-type="epub">1524-4539</issn></journal-meta><article-meta><article-id pub-id-type="pmid">20855662</article-id><article-id pub-id-type="pmc">2989430</article-id><article-id pub-id-type="doi">10.1161/CIRCULATIONAHA.110.941468</article-id><article-id pub-id-type="manuscript">NIHMS237119</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Podoplanin-expressing Cells Derived from Bone Marrow Play a Crucial Role in Postnatal Lymphatic Neovascularization</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Ji Yoon</given-names></name><degrees>MS</degrees><xref ref-type="aff" rid="A1">1</xref><xref ref-type="author-notes" rid="FN1">4</xref></contrib><contrib contrib-type="author"><name><surname>Park</surname><given-names>Changwon</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A1">1</xref><xref ref-type="author-notes" rid="FN1">4</xref><xref ref-type="author-notes" rid="FN2">5</xref></contrib><contrib contrib-type="author"><name><surname>Cho</surname><given-names>Yong Pil</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Eugine</given-names></name><degrees>BS</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Hyongbum</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kim</surname><given-names>Pilhan</given-names></name><degrees>Ph.D</degrees><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Yun</surname><given-names>Seok H.</given-names></name><degrees>Ph.D</degrees><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Yoon</surname><given-names>Young-sup</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib></contrib-group><aff id="A1"><label>1</label>Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, 30322, USA</aff><aff id="A2"><label>2</label>Department of Vascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-2dong, Songpa-gu, Seoul 138-736, Korea</aff><aff id="A3"><label>3</label>Harvard Medical School and Massachusetts General Hospital, Wellman Center for Photomedicine, Boston, Massachusetts 02114, USA</aff><author-notes><corresp id="cor1"><bold>Address correspondence to:</bold> Young-sup Yoon, M.D., Ph.D., Division of Cardiology, Department of Medicine, Emory University School of Medicine, 1639 Pierce drive, WMB 3009, Atlanta, GA 30322, Phone: 404-727-8176, Fax: 404-727-3988, <email>yyoon5@emory.edu</email></corresp><fn id="FN1" fn-type="equal"><label>4</label><p id="P1">These authors contributed equally to this work.</p></fn><fn id="FN2" fn-type="present-address"><label>5</label><p id="P2">Present address: Washington University School of Medicine, St. Louis, MO 63110, USA</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>27</day><month>10</month><year>2010</year></pub-date><pub-date pub-type="epub"><day>20</day><month>9</month><year>2010</year></pub-date><pub-date pub-type="ppub"><day>5</day><month>10</month><year>2010</year></pub-date><pub-date pub-type="pmc-release"><day>5</day><month>10</month><year>2011</year></pub-date><volume>122</volume><issue>14</issue><fpage>1413</fpage><lpage>1425</lpage><abstract><sec id="S1"><title>Background</title><p id="P3">Emerging evidence has suggested a contribution of bone marrow (BM) cells to lymphatic vessel formation; however, the exact phenotype of the cells with lymphatic endothelial progenitor cell (LEPC) function has yet to be identified. Here we investigate the identity of BM-derived LEPCs and their role in lymphatic neovascularization.</p></sec><sec sec-type="methods" id="S2"><title>Methods and Results</title><p id="P4">Culture of BM-mononuclear cells (MNCs) in the presence of VEGFA, VEGFC and EGF resulted in expression of lymphatic endothelial cell (LEC) markers. Among these cells, podoplanin<sup>+</sup> cells were isolated by magnetic-labeled cell separation system (MACS) and characterized by FACS and immunocytochemistry. These podoplanin<sup>+</sup> cells highly express markers for LECs, hematopoietic lineages, and stem/progenitor cells, and upon further cultivation, generate LECs. We further confirmed that podoplanin<sup>+</sup> cells exist in small numbers in BM and peripheral blood (PB) of normal mice, but are significantly (15 fold) augmented upon lymphangiogenic stimuli such as tumor implantation. Next, to evaluate the potential of podoplanin<sup>+</sup> cells for the formation of new lymphatic vessels <italic>in vivo</italic>, we injected culture-isolated or freshly isolated BM-derived podoplanin+ cells into wound and tumor models. Immunohistochemistry demonstrated that the injected cells were incorporated into the lymphatic vasculature, displayed LEC phenotypes, and increased lymphatic vascular density in tissues, suggesting lymphvasculogenesis. Podoplanin<sup>+</sup> cells also expressed high levels of lymphangiogenic cytokines and increased proliferation of LECs during co-culture, suggesting a lymphangiogenic or paracrine role.</p></sec><sec id="S3"><title>Conclusions</title><p id="P5">Our results provide compelling evidence that BM-derived podoplanin<sup>+</sup> cells, a previously unrecognized cell type, function as LEPCs and participate in postnatal lymphatic neovascularization through both lymphvasculogenesis and lymphangiogenesis.</p></sec></abstract><kwd-group><kwd>Bone Marrow</kwd><kwd>Podoplanin</kwd><kwd>Lymphangiogenesis</kwd><kwd>Lymphvasculogenesis</kwd></kwd-group><contract-num rid="GM1">RC1 GM092035-01
||GM</contract-num><contract-num rid="HL1">R21 HL097353-02
||HL</contract-num><contract-num rid="HL1">R01 HL084471-06
||HL</contract-num><contract-sponsor id="GM1">National Institute of General Medical Sciences : NIGMS</contract-sponsor><contract-sponsor id="HL1">National Heart, Lung, and Blood Institute : NHLBI</contract-sponsor></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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