Feasibility of Treating Irradiated Bone with Intramedullary Delivered Autologous Mesenchymal Stem Cells
Identifieur interne : 004023 ( Pmc/Corpus ); précédent : 004022; suivant : 004024Feasibility of Treating Irradiated Bone with Intramedullary Delivered Autologous Mesenchymal Stem Cells
Auteurs : Bérengère Phulpin ; Gilles Dolivet ; Pierre-Yves Marie ; Sylvain Poussier ; Sandrine Huger ; Pierre Bravetti ; Pierre Graff ; Jean-Louis Merlin ; Nguyen TranSource :
- Journal of Biomedicine and Biotechnology [ 1110-7243 ] ; 2011.
Abstract
Url:
DOI: 10.1155/2011/560257
PubMed: 21941433
PubMed Central: 3163406
Links to Exploration step
PMC:3163406Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Feasibility of Treating Irradiated Bone with Intramedullary Delivered Autologous Mesenchymal Stem Cells</title><author><name sortKey="Phulpin, Berengere" sort="Phulpin, Berengere" uniqKey="Phulpin B" first="Bérengère" last="Phulpin">Bérengère Phulpin</name><affiliation><nlm:aff>NONE</nlm:aff></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Dolivet, Gilles" sort="Dolivet, Gilles" uniqKey="Dolivet G" first="Gilles" last="Dolivet">Gilles Dolivet</name><affiliation><nlm:aff>NONE</nlm:aff></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Marie, Pierre Yves" sort="Marie, Pierre Yves" uniqKey="Marie P" first="Pierre-Yves" last="Marie">Pierre-Yves Marie</name><affiliation><nlm:aff id="I3">NancyClotep, INSERM U961, Faculty of Medicine, UHP Nancy-University, avenue de la forêt de Haye, 54500 Vandoeuvre-lès-Nancy, France</nlm:aff></affiliation></author><author><name sortKey="Poussier, Sylvain" sort="Poussier, Sylvain" uniqKey="Poussier S" first="Sylvain" last="Poussier">Sylvain Poussier</name><affiliation><nlm:aff id="I3">NancyClotep, INSERM U961, Faculty of Medicine, UHP Nancy-University, avenue de la forêt de Haye, 54500 Vandoeuvre-lès-Nancy, France</nlm:aff></affiliation></author><author><name sortKey="Huger, Sandrine" sort="Huger, Sandrine" uniqKey="Huger S" first="Sandrine" last="Huger">Sandrine Huger</name><affiliation><nlm:aff id="I4">Radiotherapy Department, Centre Alexis Vautrin, avenue de Bourgogne, Brabois, 54511 Vandoeuvre-lès-Nancy, France</nlm:aff></affiliation></author><author><name sortKey="Bravetti, Pierre" sort="Bravetti, Pierre" uniqKey="Bravetti P" first="Pierre" last="Bravetti">Pierre Bravetti</name><affiliation><nlm:aff id="I5">Oral Surgery Department, Faculty of Dentistry, 96 avenue Mal de Lattre de Tassigny BP.50208, 54004 Nancy, France</nlm:aff></affiliation></author><author><name sortKey="Graff, Pierre" sort="Graff, Pierre" uniqKey="Graff P" first="Pierre" last="Graff">Pierre Graff</name><affiliation><nlm:aff id="I4">Radiotherapy Department, Centre Alexis Vautrin, avenue de Bourgogne, Brabois, 54511 Vandoeuvre-lès-Nancy, France</nlm:aff></affiliation></author><author><name sortKey="Merlin, Jean Louis" sort="Merlin, Jean Louis" uniqKey="Merlin J" first="Jean-Louis" last="Merlin">Jean-Louis Merlin</name><affiliation><nlm:aff id="I2">Tumor Biology Unit, EA 4421 SIGReTO, UHP Nancy-University and Centre Alexis Vautrin, avenue de Bourgogne, Brabois, 54511 Vandoeuvre-lès- Nancy, France</nlm:aff></affiliation></author><author><name sortKey="Tran, Nguyen" sort="Tran, Nguyen" uniqKey="Tran N" first="Nguyen" last="Tran">Nguyen Tran</name><affiliation><nlm:aff>NONE</nlm:aff></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">21941433</idno><idno type="pmc">3163406</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3163406</idno><idno type="RBID">PMC:3163406</idno><idno type="doi">10.1155/2011/560257</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">004023</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">004023</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Feasibility of Treating Irradiated Bone with Intramedullary Delivered Autologous Mesenchymal Stem Cells</title><author><name sortKey="Phulpin, Berengere" sort="Phulpin, Berengere" uniqKey="Phulpin B" first="Bérengère" last="Phulpin">Bérengère Phulpin</name><affiliation><nlm:aff>NONE</nlm:aff></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Dolivet, Gilles" sort="Dolivet, Gilles" uniqKey="Dolivet G" first="Gilles" last="Dolivet">Gilles Dolivet</name><affiliation><nlm:aff>NONE</nlm:aff></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author><author><name sortKey="Marie, Pierre Yves" sort="Marie, Pierre Yves" uniqKey="Marie P" first="Pierre-Yves" last="Marie">Pierre-Yves Marie</name><affiliation><nlm:aff id="I3">NancyClotep, INSERM U961, Faculty of Medicine, UHP Nancy-University, avenue de la forêt de Haye, 54500 Vandoeuvre-lès-Nancy, France</nlm:aff></affiliation></author><author><name sortKey="Poussier, Sylvain" sort="Poussier, Sylvain" uniqKey="Poussier S" first="Sylvain" last="Poussier">Sylvain Poussier</name><affiliation><nlm:aff id="I3">NancyClotep, INSERM U961, Faculty of Medicine, UHP Nancy-University, avenue de la forêt de Haye, 54500 Vandoeuvre-lès-Nancy, France</nlm:aff></affiliation></author><author><name sortKey="Huger, Sandrine" sort="Huger, Sandrine" uniqKey="Huger S" first="Sandrine" last="Huger">Sandrine Huger</name><affiliation><nlm:aff id="I4">Radiotherapy Department, Centre Alexis Vautrin, avenue de Bourgogne, Brabois, 54511 Vandoeuvre-lès-Nancy, France</nlm:aff></affiliation></author><author><name sortKey="Bravetti, Pierre" sort="Bravetti, Pierre" uniqKey="Bravetti P" first="Pierre" last="Bravetti">Pierre Bravetti</name><affiliation><nlm:aff id="I5">Oral Surgery Department, Faculty of Dentistry, 96 avenue Mal de Lattre de Tassigny BP.50208, 54004 Nancy, France</nlm:aff></affiliation></author><author><name sortKey="Graff, Pierre" sort="Graff, Pierre" uniqKey="Graff P" first="Pierre" last="Graff">Pierre Graff</name><affiliation><nlm:aff id="I4">Radiotherapy Department, Centre Alexis Vautrin, avenue de Bourgogne, Brabois, 54511 Vandoeuvre-lès-Nancy, France</nlm:aff></affiliation></author><author><name sortKey="Merlin, Jean Louis" sort="Merlin, Jean Louis" uniqKey="Merlin J" first="Jean-Louis" last="Merlin">Jean-Louis Merlin</name><affiliation><nlm:aff id="I2">Tumor Biology Unit, EA 4421 SIGReTO, UHP Nancy-University and Centre Alexis Vautrin, avenue de Bourgogne, Brabois, 54511 Vandoeuvre-lès- Nancy, France</nlm:aff></affiliation></author><author><name sortKey="Tran, Nguyen" sort="Tran, Nguyen" uniqKey="Tran N" first="Nguyen" last="Tran">Nguyen Tran</name><affiliation><nlm:aff>NONE</nlm:aff></affiliation><affiliation><nlm:aff>NONE</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Biomedicine and Biotechnology</title><idno type="ISSN">1110-7243</idno><idno type="eISSN">1110-7251</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><italic>Background</italic>. We aimed to explore (i) the short-term retention of intramedullary implanted mesenchymal stem cells BMSCs and (ii) their impact on the bone blood flow and metabolism in a rat model of hindlimb irradiation. <italic>Methods</italic>. Three months after 30 Gy irradiation, fourteen animals were referred into 2 groups: a sham-operated group (<italic>n</italic> = 6) and a treated group (<italic>n</italic> = 8) in which <sup>111</sup>In-labelled BMSCs (2 × 10<sup>6</sup> cells) were injected in irradiated tibias. Bone blood flow and metabolism were assessed by serial <sup>99m</sup>Tc-HDP scintigraphy and 1-wk cell retention by recordings of <sup>99m</sup>Tc/<sup>111</sup>In activities. <italic>Results</italic>. The amount of intramedullary implanted BMSCs was of 70% at 2 H, 40% at 48 H, and 38% at 168 H. Bone blood flow and bone metabolism were significantly increased during the first week after cell transplantation, but these effects were found to reduce at 2-mo followup. <italic>Conclusion</italic>. Short-term cell retention produced concomitant enhancement in irradiated bone blood flow and metabolism.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Stone, Hb" uniqKey="Stone H">HB Stone</name></author><author><name sortKey="Coleman, Cn" uniqKey="Coleman C">CN Coleman</name></author><author><name sortKey="Anscher, Ms" uniqKey="Anscher M">MS Anscher</name></author><author><name sortKey="Mcbride, Wh" uniqKey="Mcbride W">WH McBride</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Engleman, Ma" uniqKey="Engleman M">MA Engleman</name></author><author><name sortKey="Woloschak, G" uniqKey="Woloschak G">G Woloschak</name></author><author><name sortKey="Small, W" uniqKey="Small W">W Small</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reuther, T" uniqKey="Reuther T">T Reuther</name></author><author><name sortKey="Schuster, T" uniqKey="Schuster T">T Schuster</name></author><author><name sortKey="Mende, U" uniqKey="Mende U">U Mende</name></author><author><name sortKey="Kubler, Ac" uniqKey="Kubler A">AC Kübler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jereczek Fossa, Ba" uniqKey="Jereczek Fossa B">BA Jereczek-Fossa</name></author><author><name sortKey="Orecchia, R" uniqKey="Orecchia R">R Orecchia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chrcanovic, Br" uniqKey="Chrcanovic B">BR Chrcanovic</name></author><author><name sortKey="Reher, P" uniqKey="Reher P">P Reher</name></author><author><name sortKey="Sousa, Aa" uniqKey="Sousa A">AA Sousa</name></author><author><name sortKey="Harris, M" uniqKey="Harris M">M Harris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Iwase, T" uniqKey="Iwase T">T Iwase</name></author><author><name sortKey="Nagaya, N" uniqKey="Nagaya N">N Nagaya</name></author><author><name sortKey="Fujii, T" uniqKey="Fujii T">T Fujii</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tran, N" uniqKey="Tran N">N Tran</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author><author><name sortKey="Maskali, F" uniqKey="Maskali F">F Maskali</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tran, N" uniqKey="Tran N">N Tran</name></author><author><name sortKey="Poussier, S" uniqKey="Poussier S">S Poussier</name></author><author><name sortKey="Franken, Pr" uniqKey="Franken P">PR Franken</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Muraglia, A" uniqKey="Muraglia A">A Muraglia</name></author><author><name sortKey="Martin, I" uniqKey="Martin I">I Martin</name></author><author><name sortKey="Cancedda, R" uniqKey="Cancedda R">R Cancedda</name></author><author><name sortKey="Quarto, R" uniqKey="Quarto R">R Quarto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="He, Y" uniqKey="He Y">Y He</name></author><author><name sortKey="Zhang, Zy" uniqKey="Zhang Z">ZY Zhang</name></author><author><name sortKey="Zhu, Hg" uniqKey="Zhu H">HG Zhu</name></author><author><name sortKey="Qiu, W" uniqKey="Qiu W">W Qiu</name></author><author><name sortKey="Jiang, X" uniqKey="Jiang X">X Jiang</name></author><author><name sortKey="Guo, W" uniqKey="Guo W">W Guo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kudo, K" uniqKey="Kudo K">K Kudo</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name></author><author><name sortKey="Takahashi, K" uniqKey="Takahashi K">K Takahashi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Semont, A" uniqKey="Semont A">A Sémont</name></author><author><name sortKey="Mouiseddine, M" uniqKey="Mouiseddine M">M Mouiseddine</name></author><author><name sortKey="Francois, A" uniqKey="Francois A">A François</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agay, D" uniqKey="Agay D">D Agay</name></author><author><name sortKey="Scherthan, H" uniqKey="Scherthan H">H Scherthan</name></author><author><name sortKey="Forcheron, F" uniqKey="Forcheron F">F Forcheron</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Francois, S" uniqKey="Francois S">S François</name></author><author><name sortKey="Bensidhoum, M" uniqKey="Bensidhoum M">M Bensidhoum</name></author><author><name sortKey="Mouiseddine, M" uniqKey="Mouiseddine M">M Mouiseddine</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Francois, S" uniqKey="Francois S">S François</name></author><author><name sortKey="Mouiseddine, M" uniqKey="Mouiseddine M">M Mouiseddine</name></author><author><name sortKey="Mathieu, N" uniqKey="Mathieu N">N Mathieu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hu, Kx" uniqKey="Hu K">KX Hu</name></author><author><name sortKey="Sun, Qy" uniqKey="Sun Q">QY Sun</name></author><author><name sortKey="Guo, M" uniqKey="Guo M">M Guo</name></author><author><name sortKey="Ai, Hs" uniqKey="Ai H">HS Ai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Phulpin, B" uniqKey="Phulpin B">B Phulpin</name></author><author><name sortKey="Dolivet, G" uniqKey="Dolivet G">G Dolivet</name></author><author><name sortKey="Marie, P Y" uniqKey="Marie P">P-Y Marie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schirrmeister, H" uniqKey="Schirrmeister H">H Schirrmeister</name></author><author><name sortKey="Guhlmann, A" uniqKey="Guhlmann A">A Guhlmann</name></author><author><name sortKey="Kotzerke, J" uniqKey="Kotzerke J">J Kotzerke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tran, N" uniqKey="Tran N">N Tran</name></author><author><name sortKey="Franken, Pr" uniqKey="Franken P">PR Franken</name></author><author><name sortKey="Maskali, F" uniqKey="Maskali F">F Maskali</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name></author><author><name sortKey="Tran, N" uniqKey="Tran N">N Tran</name></author><author><name sortKey="Chen, Hq" uniqKey="Chen H">HQ Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dominici, M" uniqKey="Dominici M">M Dominici</name></author><author><name sortKey="Le Blanc, K" uniqKey="Le Blanc K">K Le Blanc</name></author><author><name sortKey="Mueller, I" uniqKey="Mueller I">I Mueller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hou, C" uniqKey="Hou C">C Hou</name></author><author><name sortKey="Wu, X" uniqKey="Wu X">X Wu</name></author><author><name sortKey="Jin, X" uniqKey="Jin X">X Jin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Coppes, Rp" uniqKey="Coppes R">RP Coppes</name></author><author><name sortKey="Van Der Goot, A" uniqKey="Van Der Goot A">A van der Goot</name></author><author><name sortKey="Lombaert, Ima" uniqKey="Lombaert I">IMA Lombaert</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bey, E" uniqKey="Bey E">E Bey</name></author><author><name sortKey="Prat, M" uniqKey="Prat M">M Prat</name></author><author><name sortKey="Duhamel, P" uniqKey="Duhamel P">P Duhamel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Becker, W" uniqKey="Becker W">W Becker</name></author><author><name sortKey="Meller, J" uniqKey="Meller J">J Meller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Blocklet, D" uniqKey="Blocklet D">D Blocklet</name></author><author><name sortKey="Toungouz, M" uniqKey="Toungouz M">M Toungouz</name></author><author><name sortKey="Kiss, R" uniqKey="Kiss R">R Kiss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bohnen, Ni" uniqKey="Bohnen N">NI Bohnen</name></author><author><name sortKey="Charron, M" uniqKey="Charron M">M Charron</name></author><author><name sortKey="Reyes, J" uniqKey="Reyes J">J Reyes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takemiya, K" uniqKey="Takemiya K">K Takemiya</name></author><author><name sortKey="Kai, H" uniqKey="Kai H">H Kai</name></author><author><name sortKey="Yasukawa, H" uniqKey="Yasukawa H">H Yasukawa</name></author><author><name sortKey="Tahara, N" uniqKey="Tahara N">N Tahara</name></author><author><name sortKey="Kato, S" uniqKey="Kato S">S Kato</name></author><author><name sortKey="Imaizumi, T" uniqKey="Imaizumi T">T Imaizumi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kuyama, J" uniqKey="Kuyama J">J Kuyama</name></author><author><name sortKey="Mccormack, A" uniqKey="Mccormack A">A McCormack</name></author><author><name sortKey="George, Ajt" uniqKey="George A">AJT George</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marino, R" uniqKey="Marino R">R Marino</name></author><author><name sortKey="Martinez, C" uniqKey="Martinez C">C Martinez</name></author><author><name sortKey="Boyd, K" uniqKey="Boyd K">K Boyd</name></author><author><name sortKey="Dominici, M" uniqKey="Dominici M">M Dominici</name></author><author><name sortKey="Hofmann, Tj" uniqKey="Hofmann T">TJ Hofmann</name></author><author><name sortKey="Horwitz, Em" uniqKey="Horwitz E">EM Horwitz</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abdallah, Bm" uniqKey="Abdallah B">BM Abdallah</name></author><author><name sortKey="Kassem, M" uniqKey="Kassem M">M Kassem</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Martin, M" uniqKey="Martin M">M Martin</name></author><author><name sortKey="Delanian, S" uniqKey="Delanian S">S Delanian</name></author><author><name sortKey="Sivan, V" uniqKey="Sivan V">V Sivan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Geris, L" uniqKey="Geris L">L Geris</name></author><author><name sortKey="Gerisch, A" uniqKey="Gerisch A">A Gerisch</name></author><author><name sortKey="Sloten, Jv" uniqKey="Sloten J">JV Sloten</name></author><author><name sortKey="Weiner, R" uniqKey="Weiner R">R Weiner</name></author><author><name sortKey="Oosterwyck, Hv" uniqKey="Oosterwyck H">HV Oosterwyck</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Phulpin, B" uniqKey="Phulpin B">B Phulpin</name></author><author><name sortKey="Gangloff, P" uniqKey="Gangloff P">P Gangloff</name></author><author><name sortKey="Tran, N" uniqKey="Tran N">N Tran</name></author><author><name sortKey="Bravetti, P" uniqKey="Bravetti P">P Bravetti</name></author><author><name sortKey="Merlin, Jl" uniqKey="Merlin J">JL Merlin</name></author><author><name sortKey="Dolivet, G" uniqKey="Dolivet G">G Dolivet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mendonca, Jj" uniqKey="Mendonca J">JJ Mendonça</name></author><author><name sortKey="Juiz Lopez, P" uniqKey="Juiz Lopez P">P Juiz-Lopez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Basciano, L" uniqKey="Basciano L">L Basciano</name></author><author><name sortKey="Nemos, C" uniqKey="Nemos C">C Nemos</name></author><author><name sortKey="Foliguet, B" uniqKey="Foliguet B">B Foliguet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Holzwarth, C" uniqKey="Holzwarth C">C Holzwarth</name></author><author><name sortKey="Vaegler, M" uniqKey="Vaegler M">M Vaegler</name></author><author><name sortKey="Gieseke, F" uniqKey="Gieseke F">F Gieseke</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Biomed Biotechnol</journal-id><journal-id journal-id-type="publisher-id">JBB</journal-id><journal-title-group><journal-title>Journal of Biomedicine and Biotechnology</journal-title></journal-title-group><issn pub-type="ppub">1110-7243</issn><issn pub-type="epub">1110-7251</issn><publisher><publisher-name>Hindawi Publishing Corporation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">21941433</article-id><article-id pub-id-type="pmc">3163406</article-id><article-id pub-id-type="doi">10.1155/2011/560257</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title>Feasibility of Treating Irradiated Bone with Intramedullary Delivered Autologous Mesenchymal Stem Cells</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Phulpin</surname><given-names>Bérengère</given-names></name><xref ref-type="aff" rid="I1"><sup>1, 2</sup></xref><xref ref-type="aff" rid="I2"></xref></contrib><contrib contrib-type="author"><name><surname>Dolivet</surname><given-names>Gilles</given-names></name><xref ref-type="aff" rid="I1"><sup>1, 2</sup></xref><xref ref-type="aff" rid="I2"></xref></contrib><contrib contrib-type="author"><name><surname>Marie</surname><given-names>Pierre-Yves</given-names></name><xref ref-type="aff" rid="I3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Poussier</surname><given-names>Sylvain</given-names></name><xref ref-type="aff" rid="I3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Huger</surname><given-names>Sandrine</given-names></name><xref ref-type="aff" rid="I4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bravetti</surname><given-names>Pierre</given-names></name><xref ref-type="aff" rid="I5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Graff</surname><given-names>Pierre</given-names></name><xref ref-type="aff" rid="I4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Merlin</surname><given-names>Jean-Louis</given-names></name><xref ref-type="aff" rid="I2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tran</surname><given-names>Nguyen</given-names></name><xref ref-type="aff" rid="I3"><sup>3, 6</sup></xref><xref ref-type="aff" rid="I6"></xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="I1"><sup>1</sup>Head and Neck Surgery and Dental Units, Oncologic Surgery Department, Centre Alexis Vautrin, avenue de Bourgogne, Brabois, 54511 Vandoeuvre-lès-Nancy, France</aff><aff id="I2"><sup>2</sup>Tumor Biology Unit, EA 4421 SIGReTO, UHP Nancy-University and Centre Alexis Vautrin, avenue de Bourgogne, Brabois, 54511 Vandoeuvre-lès- Nancy, France</aff><aff id="I3"><sup>3</sup>NancyClotep, INSERM U961, Faculty of Medicine, UHP Nancy-University, avenue de la forêt de Haye, 54500 Vandoeuvre-lès-Nancy, France</aff><aff id="I4"><sup>4</sup>Radiotherapy Department, Centre Alexis Vautrin, avenue de Bourgogne, Brabois, 54511 Vandoeuvre-lès-Nancy, France</aff><aff id="I5"><sup>5</sup>Oral Surgery Department, Faculty of Dentistry, 96 avenue Mal de Lattre de Tassigny BP.50208, 54004 Nancy, France</aff><aff id="I6"><sup>6</sup>School of Surgery, INSERM U961, Faculty of Medicine, UHP Nancy-University, avenue de la forêt de Haye, 54500 Vandoeuvre-lès-Nancy, France</aff><author-notes><corresp id="cor1">*Nguyen Tran: <email>nguyen.tran@medecine.uhp-nancy.fr</email></corresp><fn fn-type="other"><p>Academic Editor: Ji Wu</p></fn></author-notes><pub-date pub-type="ppub"><year>2011</year></pub-date><pub-date pub-type="epub"><day>29</day><month>8</month><year>2011</year></pub-date><volume>2011</volume><elocation-id>560257</elocation-id><history><date date-type="received"><day>3</day><month>5</month><year>2011</year></date><date date-type="accepted"><day>20</day><month>6</month><year>2011</year></date></history><permissions><copyright-statement>Copyright © 2011 Bérengère Phulpin et al.</copyright-statement><copyright-year>2011</copyright-year><license license-type="open-access"><license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p><italic>Background</italic>. We aimed to explore (i) the short-term retention of intramedullary implanted mesenchymal stem cells BMSCs and (ii) their impact on the bone blood flow and metabolism in a rat model of hindlimb irradiation. <italic>Methods</italic>. Three months after 30 Gy irradiation, fourteen animals were referred into 2 groups: a sham-operated group (<italic>n</italic> = 6) and a treated group (<italic>n</italic> = 8) in which <sup>111</sup>In-labelled BMSCs (2 × 10<sup>6</sup> cells) were injected in irradiated tibias. Bone blood flow and metabolism were assessed by serial <sup>99m</sup>Tc-HDP scintigraphy and 1-wk cell retention by recordings of <sup>99m</sup>Tc/<sup>111</sup>In activities. <italic>Results</italic>. The amount of intramedullary implanted BMSCs was of 70% at 2 H, 40% at 48 H, and 38% at 168 H. Bone blood flow and bone metabolism were significantly increased during the first week after cell transplantation, but these effects were found to reduce at 2-mo followup. <italic>Conclusion</italic>. Short-term cell retention produced concomitant enhancement in irradiated bone blood flow and metabolism.</p></abstract></article-meta></front><body><sec id="sec1"><title>1. Introduction</title><p>Radiotherapy has been proven to successfully treat local and regional neoplasic lesions but it may adversely impact on normal tissues [<xref ref-type="bibr" rid="B1">1</xref>]. High vulnerability to irradiation was already documented in various bone tissues (pelvis, sternum, vertebra, clavicle, femoral head, and mandible) [<xref ref-type="bibr" rid="B2">2</xref>] with subsequent deleterious effect on the bone metabolism and healing leading thereafter to infection, atrophy, pathological fractures, and osteoradionecrosis. For instance, the incidence of osteoradionecrosis after conventional radiotherapy ranges from 0.9% to 35% [<xref ref-type="bibr" rid="B3">3</xref>], with an increased risk when doses given to the mandible exceed 60 Gy [<xref ref-type="bibr" rid="B4">4</xref>]. Thus, irradiation of the mandible represents the most devastating radiotherapy-induced complication and might sometimes lead to surgical resection [<xref ref-type="bibr" rid="B5">5</xref>].</p><p>Since vascular ischemia is one of predictors of postirradiation degeneration, the inception of angiogenesis by implantation of bone marrow mesenchymal stem cells (BMSCs) might represent a therapeutic approach for rehabilitating the irradiated bone tissue. Such potentiality was already documented in diverse ischemic pathologies such as hindlimb ischemia [<xref ref-type="bibr" rid="B6">6</xref>] or myocardial infarction [<xref ref-type="bibr" rid="B7">7</xref>, <xref ref-type="bibr" rid="B8">8</xref>]. Previous data regarding the role of BMSCs in the bone reconstruction have outlined their active contribution in the bone formation when seeded on various scaffolds [<xref ref-type="bibr" rid="B9">9</xref>, <xref ref-type="bibr" rid="B10">10</xref>]. In a dog model of mandible segmental defect, the feasibility of bone reconstruction using morphologic and 3-D beta-tricalcium phosphate scaffold seeded with autologous BMSCs was highlighted by both bone formation and bone vascularization [<xref ref-type="bibr" rid="B10">10</xref>].</p><p>Experiments with BMSCs in the treatment or the prevention of radio-induced damage were reported on intestine [<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B12">12</xref>] and skin [<xref ref-type="bibr" rid="B13">13</xref>–<xref ref-type="bibr" rid="B15">15</xref>] using systemic [<xref ref-type="bibr" rid="B14">14</xref>–<xref ref-type="bibr" rid="B16">16</xref>] or local [<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B13">13</xref>] delivery. Little is known however about the effect of BMSCs in irradiated bone tissue, and especially, the bioavailability and biodistribution of these cells within the targeted areas since their in vivo monitoring is now mandatory to further understand their benefice.</p><p>The study was designed to explore, in a rat model of hindlimb irradiation, the feasibility of rehabilitating irradiated tibial bone tissue by intramedullary implanted BMSCs. The assessment of BMSCs' retention and distribution were conducted up to 7 days following transplantation using <sup>111</sup>In-oxine-labeling technique. Therapeutic effect on bone perfusion and metabolism was determined by serial <sup>99m-</sup>technetium hydroxymethane diphosphonate (<sup>99m</sup>Tc-HDP) planar scintigraphy.</p></sec><sec id="sec2"><title>2. Materials and Methods</title><sec sec-type="subsection" id="sec2.1"><title>2.1. Animals</title><p>This study was conducted in 14 Wistar rats (initial body-weight of 410 g–460 g). All experimental procedures were in accordance with our local ethical committee and with the regulations of the Animal Welfare Act of the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publication no. 85-23, Revised 1996).</p><p>Three months after experiencing a hindlimb irradiation with a monodose of 30 Gy a <sup>99m</sup>Tc-HDP scintigraphy was performed. Thereafter, animals were referred into 2 groups: a control sham-operated group (<italic>n</italic> = 6) and a treated group (<italic>n</italic> = 8) in which <sup>111</sup>In-labelled BMSCs (2 × 10<sup>6</sup> cells) were intramedullary injected in irradiated tibial diaphysis; BMSCs being harvested before irradiation were cultured until passage 4, and their mesenchymal phenotypes were evidenced by flow cytometry. </p><p>To evaluate changes in bone blood flow and metabolism, serial <sup>99m</sup>Tc-HDP planar scintigraphy was scheduled at 3 months after irradiation and at 2 months after the cell therapy. The early cell retention after the cell therapy was assessed by additional dual recordings of <sup>99m</sup>Tc/<sup>111</sup>in activities done at 2 hours, 48 hours, and 168 hours after the cell injection.</p></sec><sec sec-type="subsection" id="sec2.2"><title>2.2. Irradiation Procedures</title><p>Irradiation of the hindlimb was performed under general anesthesia as previously described [<xref ref-type="bibr" rid="B17">17</xref>]. Briefly, the animals were placed in prone position upon a thick polystyrene phantom and their hindlimb was immobilized by adhesive tape. The focus skin distance was 70 cm, and the field size was 20 × 30 cm. The collimating block was positioned on a 0.5 cm thick acrylic platform to shield the body and only irradiated the exposition of the left hindlimb without the pelvis. Radiation with <sup>60</sup>Co was delivered in a vertical beam from a Theratron 780C X-ray machine delivering gamma rays of 1.25 MeV energy and dose rate of 1.4 Gy/min.</p></sec><sec sec-type="subsection" id="sec2.3"><title>2.3. Noninvasive Imaging Procedures</title><sec sec-type="subsubsection" id="sec2.3.1"><title>2.3.1. Sequential Planar Scintigraphy</title><p>Bone blood flow and metabolism were assessed using <sup>99m</sup>Tc-HDP. After the intravenous injection of 9 mCi of <sup>99m</sup>Tc-HDP and under general anesthesia, the acquisition was recorded using a single-head gamma camera (Sopha DSX, SMV-GE) equipped with a 1.5 mm pinhole collimator (165 mm focal length, 44 mm radius of rotation) and with the following parameters: 256 × 256 matrix, 1.14 zoom, and 140 (±20%) keV energy window. Two acquisitions were performed: a dynamic HDP uptake (blood flow) consisted of images obtained at 1 second intervals for 60 seconds reflecting vascularity and a delayed (3 hours after) acquisition of HDP uptake reflecting osteoblastic metabolism [<xref ref-type="bibr" rid="B18">18</xref>].</p><p>Changes in accumulation of the tracer in irradiated bone and surrounding tissues were evaluated by measuring uptake within regions of interest (ROI) on the computer-processed images software (Dysplay, Console Vision, General Electric). Values were expressed as percentage (%) of total body activity.</p></sec><sec sec-type="subsubsection" id="sec2.3.2"><title>2.3.2. Dual <sup>111</sup>In/<sup>99m</sup>Tc Scintigraphy</title><p>Planar scintigraphic images of the body distribution of <sup>111</sup>In-labeled BMSCs were provided by the same single-head gamma camera (Sopha DSX, SMV-GE) already described [<xref ref-type="bibr" rid="B8">8</xref>, <xref ref-type="bibr" rid="B19">19</xref>]. Two 20% energy windows centered on the 172 KeV and 246 KeV photopeaks of <sup>111</sup>In were applied. The initial image was recorded 2 H after cell transplantation during a 15-min period and then at day 2 (48 H) and day 7 (168 H) during time periods of 20 and 40 min, respectively. <sup>111</sup>In activity from each image was expressed relative to the total injected activity (total body activity determined at 2 H) and after additional corrections for the physical decay of <sup>111</sup>In (2.9 days).</p></sec><sec sec-type="subsubsection" id="sec2.3.3"><title>2.3.3. BMSC Isolation, Cell Culture and Flow Cytometry</title><p>Autologous bone marrow cells, harvested from the left tibias by punction, were cultured and expanded as previously described in detail elsewhere [<xref ref-type="bibr" rid="B19">19</xref>, <xref ref-type="bibr" rid="B20">20</xref>]. Briefly, aspired whole bone marrow cells were suspended in Iscove's modified Dulbecco's culture medium (Life Technologies, Cergy Pontoise, France) containing 10% fetal bovine serum (Life Technologies, Cergy Pontoise, France), 0.1 mmol/L <italic>β</italic> mercaptoethanol (Sigma, France), 100 U/mL penicillin, and 100 <italic>μ</italic>g/mL streptomycin. The cells were grown in a 5% humidified CO<sub>2</sub> atmosphere at 37°C, and the medium was changed every 2 days.</p><p>To ascertain the mesenchymal phenotype of transplanted BMSCs, the expression of CD34, CD44, CD45, and CD90 surface antigens of cells prior to implantation (passage 4) was analysed using flow cytometry method (FACSCalibur; Becton Dickinson, Meylan, France) and the Cellquest software (Becton Dickinson, Meylan, France) [<xref ref-type="bibr" rid="B20">20</xref>].</p></sec></sec><sec sec-type="subsection" id="sec2.4"><title>2.4. Intramedullary Implantation of Radiolabeled BMSCs</title><sec sec-type="subsubsection" id="sec2.4.1"><title>2.4.1. Cell Labeling and Cell Transplantation</title><p>As already described [<xref ref-type="bibr" rid="B7">7</xref>, <xref ref-type="bibr" rid="B8">8</xref>], BMSCs (2 × 10<sup>6</sup> cells/mL) were trypsinised and incubated at 37°C with 15 MBq of <sup>111</sup>In-oxine (Mallinckrodt Medical B.V., Holland) during a 10-min period, the labelling process being stopped by 5-min centrifugation at 950 g. This 10-min incubation period was previously found to result in both a sufficiently high labeling efficiency (69%) and absence of significant deterioration of cell viability (96%) [<xref ref-type="bibr" rid="B8">8</xref>].</p><p>After stab incision, a 1 mm diameter drill hole was performed perpendicularly to the orientation of the tibial cortical bone. The <sup>111</sup>In-labelled cells were conditioned in a 1 mL syringe (2 × 10<sup>6</sup> cells in 50 <italic>μ</italic>L) and were injected through the mini-invasive perforation into the bone marrow of the left tibia. To prevent leakage of transplanted cells in the surrounding tissues a biocompatible bandage (IRM Dentsply 78467 Konstanz Germany) was positioned over the drilling site.</p></sec><sec sec-type="subsubsection" id="sec2.4.2"><title>2.4.2. Statistics</title><p>The statistical analysis was carried out with the Statistical Package SPSS version 14.0 (SPSS, Inc., Chicago, Ill, USA). We used Mann-Whitney tests for the unpaired comparisons and Wilcoxon tests for the paired comparisons in each group. For each test, a <italic>P</italic> value < 0.05 was considered to be indicative of a significant difference.</p></sec></sec></sec><sec id="sec3"><title>3. Results</title><sec sec-type="subsection" id="sec3.1"><title>3.1. Animal Model of Hindlimb Irradiation and Pretherapeutic Data</title><p>No animal died throughout the study's period. The 30-Gy irradiation induced 3-4 weeks later a persisting alopecia in the irradiated hindlimb (<xref ref-type="fig" rid="fig1">Figure 1(a)</xref>) without affecting however the daily locomotor activities of those animals. </p><p>At 2-mo scintigraphic imaging, radiation-induced bone defects appear as areas of attenuation of signal intensity covering the irradiated lower limb, with pronounced effect in the tibia (see <xref ref-type="fig" rid="fig1">Figure 1(b)</xref>, e.g.,). The pretherapeutic data of the group control and the cell-treated group were resumed in the <xref ref-type="table" rid="tab1">Table 1</xref>. In both groups, compared with the total body activity, irradiation of the hindlimb produced similar alteration in tibial values of bone perfusion blood flow (early uptake of <sup>99m</sup>Tc-HDP) and bone osteoblastic metabolism (late uptake of <sup>99m</sup>Tc-HDP). For example, bone perfusion blood flow was 3.2 ± 0.8% at the irradiated tibia compared to 3.8 ± 1.0% found in the healthy one (<italic>P</italic> < 0.05). A slight decrease in bone metabolism of circa 10% was found in irradiated tibias, but values did not reach statistical significance (2.0 ± 0.3% versus 2.3 ± 0.6% found in healthy counterparts).</p></sec><sec sec-type="subsection" id="sec3.2"><title>3.2. Cell Identification, Short-Term In vivoTracking, and Posttherapeutic Data</title><sec sec-type="subsubsection" id="sec3.2.1"><title>3.2.1. Cell Identification Prior to the Cell Grafting</title><p>Flow cytometry analyses (<xref ref-type="fig" rid="fig2">Figure 2(a)</xref>) showed that the engrafted BMSCs of passage 4 expressed strong expression of CD44 and CD90 surface antigens (>80%). Thus, these cells were negative for CD45 and CD34 (percentage of positive cells were 2.41 ± 2.47% for CD45 and 1.99 ± 2.72% for CD34). These data were consistent with our previous studies [<xref ref-type="bibr" rid="B20">20</xref>] and in accordance with criteria defined by the International Society for Cellular Therapy (ISCT) [<xref ref-type="bibr" rid="B21">21</xref>].</p></sec><sec sec-type="subsubsection" id="sec3.2.2"><title>3.2.2. Effect of BMSCs on Bone Blood Flow and Bone Metabolism in Irradiated Hindlimb</title><p><sup>99m</sup>Tc-HDP scintigraphic examinations performed after intramedullary implantation of BMSCs have documented, especially in the tibial area, a significant rise in both bone blood flow and bone metabolism during the posttherapeutic first week (<xref ref-type="table" rid="tab2">Table 2</xref> and <xref ref-type="fig" rid="fig5">Figure 5</xref>). At 48 hours, the bone blood flow found in cell-treated tibias was 4.7 ± 0.7% corresponding to an enhancement of 62% compared to basal pretherapeutic values (<italic>P</italic> < 0.01). Similarly, the bone metabolism was 35% higher than that measured before treatment, values were 2.7 ± 0.5% (<italic>P</italic> < 0.01 versus pretherapeutic data). These effects persisted at 7 days, bone blood flow was 4.5 ± 1.0% (<italic>P</italic> < 0.01 versus pretherapeutic data), and bone metabolism was 2.6 ± 0.6% (<italic>P</italic> < 0.05 versus pretherapeutic data). At 2-mo followup, these uptake values were found to be down to 3.1 ± 1.4% for the bone blood flow and 1.7 ± 0.3% for the bone metabolism.</p></sec></sec></sec><sec id="sec4"><title>4. Discussion</title><p>Damage of normal tissue secondary to radiotherapy is still a major problem in cancer treatment. Stem cell therapy seems to be a new treatment option in radio-induced tissue abnormalities [<xref ref-type="bibr" rid="B22">22</xref>–<xref ref-type="bibr" rid="B24">24</xref>], providing a mean to reduce related side effects and to improve the quality of life of patients. In this study, we investigated the feasibility of BMSCs when injected intramedullary in an experimental rat model of radio-induced degeneration recently described by our group [<xref ref-type="bibr" rid="B17">17</xref>]. </p><p>In the present study, <sup>111</sup>In-oxine labelling of BMSCs was successfully used to follow bone retention and body distribution of BMSCS when injected intramedullary within irradiated bone. <sup>111</sup>In-labelled cells have been widely used in humans in localizing areas of inflammation by imaging the leukocyte distribution [<xref ref-type="bibr" rid="B25">25</xref>]. Furthermore, <sup>111</sup>In-labelling techniques have been applied in various experimental settings in animal to analyse the migration of dendritic cells [<xref ref-type="bibr" rid="B26">26</xref>], the biodistribution of transplanted hepatocytes [<xref ref-type="bibr" rid="B27">27</xref>], and of injected MSCs in animals model of heart or lung disease [<xref ref-type="bibr" rid="B7">7</xref>, <xref ref-type="bibr" rid="B28">28</xref>]. As previously described [<xref ref-type="bibr" rid="B7">7</xref>], the technique used here reached a high efficiency (69%) with a low toxicity (viability > 95%). In addition, it has been previously demonstrated that the leakage of <sup>111</sup>In from labelled cells resulted in a high <sup>111</sup>In uptake in the liver and spleen and usually had hepatobiliary and renal excretion pathways [<xref ref-type="bibr" rid="B7">7</xref>, <xref ref-type="bibr" rid="B29">29</xref>]. This is in accordance with our observations, and no <sup>111</sup>In radioactivity was found in bones outside the area of injection. Approximately 70% of grafted cells could be estimated to be retained within bone damaged area 2 hours after transplantation. The “disappearance” of radiolabeled grafted cell may be explained by the method used for BMSCs injection which could be associated with a leakage of BMSCs from the injection site before bandage and residual BMSCs in the injection syringes. These data are fully consistent with those of the study of Tran et al. [<xref ref-type="bibr" rid="B7">7</xref>], where approximately 60% of <sup>111</sup>In labeled BMSCs were still present 2 hours after direct transplantation in a necrotic rat myocardium and were retained within the heart throughout the 7 days of followup. In the present study, after 48 hours, BMSCs number decreased to approximately 40% and remained unchanged until the 7th day. The mechanism responsible for cell loss during the first two days remains to be explored. These results highlighted that at short term, the engrafted BMSCs remain localized within the area of injection into irradiated bone. </p><p>Many studies of cell therapy using mesenchymal stem cells [<xref ref-type="bibr" rid="B14">14</xref>, <xref ref-type="bibr" rid="B16">16</xref>], used the systemic injection as modality of administration. In comparison, using local injection, cells engraftment seems to be better. For example, in François et al.'s study [<xref ref-type="bibr" rid="B14">14</xref>], rats were transplanted with a dose of 5 × 10<sup>6</sup> BMSCs 24 hours after irradiation of the hindlimb at a single dose of 26.5 Gy. Fifteen days later, the implantation rates of BMSCs in bone and bone marrow were, respectively, approximately 12.5% and less than 0.25%. The major limitation of this approach is constituted by the very low number of BMSCs that home to the site of injury [<xref ref-type="bibr" rid="B30">30</xref>]. A possible reason for the inefficient engraftment and homing could be the entrapment of BMSCs in the lungs [<xref ref-type="bibr" rid="B31">31</xref>]. Moreover, vascular ischemia and fibrosis, characteristic injury of irradiated tissue [<xref ref-type="bibr" rid="B1">1</xref>, <xref ref-type="bibr" rid="B32">32</xref>], may prevent homing and engraftment of BMSCs. </p><p>After cell therapy, the bone blood flow and bone metabolism evolved similarly, and a significant increase of these values was observed during the seven days following the BMSCs engraftment. The influence of the surgical procedure used in the present study would require further investigation, especially regarding the role of the inflammation cells response and the local recruitment of mesenchymal stem cells [<xref ref-type="bibr" rid="B33">33</xref>] that should have been induced by the wound healing after drilling the cortical bone. However, the benefit obtained seems to be transient since 2 months after cell therapy, blood flow time and bone uptake of <sup>99m</sup>Tc-HDP did not differ significantly from data measured in ungrafted animals irradiated at 30 Gy. This result slightly differs from those achieved in our previous study [<xref ref-type="bibr" rid="B34">34</xref>], in which autologous fat was used as source of mesenchymal stem cell and grafted within irradiated area, inducing clinical benefit that appeared to be linked to the improvement of vascular network and disappearance of necrotic area. Additional results demonstrating the potency of BMSCs therapy in irradiated tissues were recently reported [<xref ref-type="bibr" rid="B35">35</xref>] describing a case of regenerative reconstruction of a terminal stage of osteoradionecrosis with BMSCs and progenitor cells. Another explanation that stands for the short effect of engrafted BMSCs might be related to the native hypoxic microenvironment of the medullar area target of the bone. The BMSCs used here were expanded according to most of the conventional cell culture procedures, that is, in normoxic condition (21% O<sub>2</sub>). Although they have mesenchymal characteristics, recent works from our group [<xref ref-type="bibr" rid="B36">36</xref>] and others [<xref ref-type="bibr" rid="B37">37</xref>] have suggested that BMSC, when cultured under 5% O<sub>2</sub> rather than under 21% O<sub>2</sub>, had better growth advantage in long-term cell expansion. Thus, the hypoxic BMSC expressed more adhesion and extracellular matrix molecules and displayed more plasticity features. It is then possible that different <italic>in vitro</italic> conditions during the cell selection and expansion might lower their ability to repair when reimplanted in native environment. This hypothesis needs further experimental evidences.</p></sec><sec id="sec5"><title>5. Conclusion</title><p>In conclusion, the present study shows the feasibility of the intramedullary implantation of BMSCs in the attempt to rehabilitate the irradiated bone. Our data suggested that BMSCs appear to remain around the injection site, without evident body redistribution, for at least a 7-day period along with a transient benefice on bone blood flow and bone metabolism. Further experiments are required to evaluate their long-term beneficial effect.</p></sec><sec id="sec6"><title> Conflict of Interests</title><p>The authors declare that there is no conflict of interests.</p></sec></body><back><ack><title>Acknowledgment</title><p>This work was granted by the Lorraine Comity of the French League against cancers (Ligue Française contre le cancer, Comités Lorrains).</p></ack><ref-list><ref id="B1"><label>1</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stone</surname><given-names>HB</given-names></name><name><surname>Coleman</surname><given-names>CN</given-names></name><name><surname>Anscher</surname><given-names>MS</given-names></name><name><surname>McBride</surname><given-names>WH</given-names></name></person-group><article-title>Effects of radiation on normal tissue: consequences and mechanisms</article-title><source><italic>The Lancet Oncology</italic></source><year>2003</year><volume>4</volume><issue>9</issue><fpage>529</fpage><lpage>536</lpage><pub-id pub-id-type="pmid">12965273</pub-id></element-citation></ref><ref id="B2"><label>2</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Engleman</surname><given-names>MA</given-names></name><name><surname>Woloschak</surname><given-names>G</given-names></name><name><surname>Small</surname><given-names>W</given-names><suffix>Jr.</suffix></name></person-group><article-title>Radiation-induced skeletal injury</article-title><source><italic>Cancer Treatment and Research</italic></source><year>2006</year><volume>128</volume><fpage>155</fpage><lpage>169</lpage><pub-id pub-id-type="pmid">16335017</pub-id></element-citation></ref><ref id="B3"><label>3</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Reuther</surname><given-names>T</given-names></name><name><surname>Schuster</surname><given-names>T</given-names></name><name><surname>Mende</surname><given-names>U</given-names></name><name><surname>Kübler</surname><given-names>AC</given-names></name></person-group><article-title>Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients—a report of a thirty year retrospective review</article-title><source><italic>International Journal of Oral and Maxillofacial Surgery</italic></source><year>2003</year><volume>32</volume><issue>3</issue><fpage>289</fpage><lpage>295</lpage><pub-id pub-id-type="pmid">12767877</pub-id></element-citation></ref><ref id="B4"><label>4</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jereczek-Fossa</surname><given-names>BA</given-names></name><name><surname>Orecchia</surname><given-names>R</given-names></name></person-group><article-title>Radiotherapy-induced mandibular bone complications</article-title><source><italic>Cancer Treatment Reviews</italic></source><year>2002</year><volume>28</volume><issue>1</issue><fpage>65</fpage><lpage>74</lpage><pub-id pub-id-type="pmid">12027415</pub-id></element-citation></ref><ref id="B5"><label>5</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chrcanovic</surname><given-names>BR</given-names></name><name><surname>Reher</surname><given-names>P</given-names></name><name><surname>Sousa</surname><given-names>AA</given-names></name><name><surname>Harris</surname><given-names>M</given-names></name></person-group><article-title>Osteoradionecrosis of the jaws-a current overview—part 1: physiopathology and risk and predisposing factors</article-title><source><italic>Oral and Maxillofacial Surgery</italic></source><year>2010</year><volume>14</volume><issue>1</issue><fpage>3</fpage><lpage>16</lpage><pub-id pub-id-type="pmid">20119841</pub-id></element-citation></ref><ref id="B6"><label>6</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Iwase</surname><given-names>T</given-names></name><name><surname>Nagaya</surname><given-names>N</given-names></name><name><surname>Fujii</surname><given-names>T</given-names></name><etal></etal></person-group><article-title>Comparison of angiogenic potency between mesenchymal stem cells and mononuclear cells in a rat model of hindlimb ischemia</article-title><source><italic>Cardiovascular Research</italic></source><year>2005</year><volume>66</volume><issue>3</issue><fpage>543</fpage><lpage>551</lpage><pub-id pub-id-type="pmid">15914119</pub-id></element-citation></ref><ref id="B7"><label>7</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tran</surname><given-names>N</given-names></name><name><surname>Li</surname><given-names>Y</given-names></name><name><surname>Maskali</surname><given-names>F</given-names></name><etal></etal></person-group><article-title>Short-term heart retention and distribution of intramyocardial delivered mesenchymal cells within necrotic or intact myocardium</article-title><source><italic>Cell Transplantation</italic></source><year>2006</year><volume>15</volume><issue>4</issue><fpage>351</fpage><lpage>358</lpage><pub-id pub-id-type="pmid">16898229</pub-id></element-citation></ref><ref id="B8"><label>8</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tran</surname><given-names>N</given-names></name><name><surname>Poussier</surname><given-names>S</given-names></name><name><surname>Franken</surname><given-names>PR</given-names></name><etal></etal></person-group><article-title>Feasibility of in vivo dual-energy myocardial SPECT for monitoring the distribution of transplanted cells in relation to the infarction site</article-title><source><italic>European Journal of Nuclear Medicine and Molecular Imaging</italic></source><year>2006</year><volume>33</volume><issue>6</issue><fpage>709</fpage><lpage>715</lpage><pub-id pub-id-type="pmid">16572303</pub-id></element-citation></ref><ref id="B9"><label>9</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Muraglia</surname><given-names>A</given-names></name><name><surname>Martin</surname><given-names>I</given-names></name><name><surname>Cancedda</surname><given-names>R</given-names></name><name><surname>Quarto</surname><given-names>R</given-names></name></person-group><article-title>A nude mouse model for human bone formation in unloaded conditions</article-title><source><italic>Bone</italic></source><year>1998</year><volume>22</volume><issue>5</issue><fpage>131S</fpage><lpage>134S</lpage><pub-id pub-id-type="pmid">9600769</pub-id></element-citation></ref><ref id="B10"><label>10</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>He</surname><given-names>Y</given-names></name><name><surname>Zhang</surname><given-names>ZY</given-names></name><name><surname>Zhu</surname><given-names>HG</given-names></name><name><surname>Qiu</surname><given-names>W</given-names></name><name><surname>Jiang</surname><given-names>X</given-names></name><name><surname>Guo</surname><given-names>W</given-names></name></person-group><article-title>Experimental study on reconstruction of segmental mandible defects using tissue engineered bone combined bone marrow stromal cells with three-dimensional tricalcium phosphate</article-title><source><italic>Journal of Craniofacial Surgery</italic></source><year>2007</year><volume>18</volume><issue>4</issue><fpage>800</fpage><lpage>805</lpage><pub-id pub-id-type="pmid">17667668</pub-id></element-citation></ref><ref id="B11"><label>11</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kudo</surname><given-names>K</given-names></name><name><surname>Liu</surname><given-names>Y</given-names></name><name><surname>Takahashi</surname><given-names>K</given-names></name><etal></etal></person-group><article-title>Transplantation of mesenchymal stem cells to prevent radiation-induced intestinal injury in mice</article-title><source><italic>Journal of Radiation Research</italic></source><year>2010</year><volume>51</volume><issue>1</issue><fpage>73</fpage><lpage>79</lpage><pub-id pub-id-type="pmid">19851042</pub-id></element-citation></ref><ref id="B12"><label>12</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Sémont</surname><given-names>A</given-names></name><name><surname>Mouiseddine</surname><given-names>M</given-names></name><name><surname>François</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Mesenchymal stem cells improve small intestinal integrity through regulation of endogenous epithelial cell homeostasis</article-title><source><italic>Cell Death and Differentiation</italic></source><year>2010</year><volume>17</volume><issue>6</issue><fpage>952</fpage><lpage>961</lpage><pub-id pub-id-type="pmid">20019749</pub-id></element-citation></ref><ref id="B13"><label>13</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Agay</surname><given-names>D</given-names></name><name><surname>Scherthan</surname><given-names>H</given-names></name><name><surname>Forcheron</surname><given-names>F</given-names></name><etal></etal></person-group><article-title>Multipotent mesenchymal stem cell grafting to treat cutaneous radiation syndrome: development of a new minipig model</article-title><source><italic>Experimental Hematology</italic></source><year>2010</year><volume>38</volume><issue>10</issue><fpage>945</fpage><lpage>956</lpage><pub-id pub-id-type="pmid">20600578</pub-id></element-citation></ref><ref id="B14"><label>14</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>François</surname><given-names>S</given-names></name><name><surname>Bensidhoum</surname><given-names>M</given-names></name><name><surname>Mouiseddine</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Local irradiation not only induces homing of human mesenchymal stem cells at exposed sites but promotes their widespread engraftment to multiple organs: a study of their quantitative distribution after irradiation damage</article-title><source><italic>Stem Cells</italic></source><year>2006</year><volume>24</volume><issue>4</issue><fpage>1020</fpage><lpage>1029</lpage><pub-id pub-id-type="pmid">16339642</pub-id></element-citation></ref><ref id="B15"><label>15</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>François</surname><given-names>S</given-names></name><name><surname>Mouiseddine</surname><given-names>M</given-names></name><name><surname>Mathieu</surname><given-names>N</given-names></name><etal></etal></person-group><article-title>Human mesenchymal stem cells favour healing of the cutaneous radiation syndrome in a xenogenic transplant model</article-title><source><italic>Annals of Hematology</italic></source><year>2007</year><volume>86</volume><issue>1</issue><fpage>1</fpage><lpage>8</lpage><pub-id pub-id-type="pmid">17043780</pub-id></element-citation></ref><ref id="B16"><label>16</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hu</surname><given-names>KX</given-names></name><name><surname>Sun</surname><given-names>QY</given-names></name><name><surname>Guo</surname><given-names>M</given-names></name><name><surname>Ai</surname><given-names>HS</given-names></name></person-group><article-title>The radiation protection and therapy effects of mesenchymal stem cells in mice with acute radiation injury</article-title><source><italic>British Journal of Radiology</italic></source><year>2010</year><volume>83</volume><issue>985</issue><fpage>52</fpage><lpage>58</lpage><pub-id pub-id-type="pmid">20139249</pub-id></element-citation></ref><ref id="B17"><label>17</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Phulpin</surname><given-names>B</given-names></name><name><surname>Dolivet</surname><given-names>G</given-names></name><name><surname>Marie</surname><given-names>P-Y</given-names></name><etal></etal></person-group><article-title>Re-assessment of chronic radio-induced tissue damage in a rat hindlimb model</article-title><source><italic>Experimental and Therapeutic Medicine</italic></source><year>2010</year><volume>1</volume><fpage>553</fpage><lpage>560</lpage></element-citation></ref><ref id="B18"><label>18</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schirrmeister</surname><given-names>H</given-names></name><name><surname>Guhlmann</surname><given-names>A</given-names></name><name><surname>Kotzerke</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Early detection and accurate description of extent of metastatic bone disease in breast cancer with fluoride ion and positron emission tomography</article-title><source><italic>Journal of Clinical Oncology</italic></source><year>1999</year><volume>17</volume><issue>8</issue><fpage>2381</fpage><lpage>2389</lpage><pub-id pub-id-type="pmid">10561300</pub-id></element-citation></ref><ref id="B19"><label>19</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tran</surname><given-names>N</given-names></name><name><surname>Franken</surname><given-names>PR</given-names></name><name><surname>Maskali</surname><given-names>F</given-names></name><etal></etal></person-group><article-title>Intramyocardial implantation of bone marrow-derived stem cells enhances perfusion in chronic myocardial infarction: dependency on initial perfusion depth and follow-up assessed by gated pinhole SPECT</article-title><source><italic>Journal of Nuclear Medicine</italic></source><year>2007</year><volume>48</volume><issue>3</issue><fpage>405</fpage><lpage>412</lpage><pub-id pub-id-type="pmid">17332618</pub-id></element-citation></ref><ref id="B20"><label>20</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname><given-names>L</given-names></name><name><surname>Tran</surname><given-names>N</given-names></name><name><surname>Chen</surname><given-names>HQ</given-names></name><etal></etal></person-group><article-title>Time-related changes in expression of collagen types I and III and of tenascin-C in rat bone mesenchymal stem cells under co-culture with ligament fibroblasts or uniaxial stretching</article-title><source><italic>Cell and Tissue Research</italic></source><year>2008</year><volume>332</volume><issue>1</issue><fpage>101</fpage><lpage>109</lpage><pub-id pub-id-type="pmid">18196274</pub-id></element-citation></ref><ref id="B21"><label>21</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Dominici</surname><given-names>M</given-names></name><name><surname>Le Blanc</surname><given-names>K</given-names></name><name><surname>Mueller</surname><given-names>I</given-names></name><etal></etal></person-group><article-title>Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement</article-title><source><italic>Cytotherapy</italic></source><year>2006</year><volume>8</volume><issue>4</issue><fpage>315</fpage><lpage>317</lpage><pub-id pub-id-type="pmid">16923606</pub-id></element-citation></ref><ref id="B22"><label>22</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hou</surname><given-names>C</given-names></name><name><surname>Wu</surname><given-names>X</given-names></name><name><surname>Jin</surname><given-names>X</given-names></name></person-group><article-title>Autologous bone marrow stromal cells transplantation for the treatment of secondary arm lymphedema: a prospective controlled study in patients with breast cancer related lymphedema</article-title><source><italic>Japanese Journal of Clinical Oncology</italic></source><year>2008</year><volume>38</volume><issue>10</issue><fpage>670</fpage><lpage>674</lpage><pub-id pub-id-type="pmid">18776199</pub-id></element-citation></ref><ref id="B23"><label>23</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Coppes</surname><given-names>RP</given-names></name><name><surname>van der Goot</surname><given-names>A</given-names></name><name><surname>Lombaert</surname><given-names>IMA</given-names></name></person-group><article-title>Stem cell therapy to reduce radiation-induced normal tissue damage</article-title><source><italic>Seminars in Radiation Oncology</italic></source><year>2009</year><volume>19</volume><issue>2</issue><fpage>112</fpage><lpage>121</lpage><pub-id pub-id-type="pmid">19249649</pub-id></element-citation></ref><ref id="B24"><label>24</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bey</surname><given-names>E</given-names></name><name><surname>Prat</surname><given-names>M</given-names></name><name><surname>Duhamel</surname><given-names>P</given-names></name><etal></etal></person-group><article-title>Emerging therapy for improving wound repair of severe radiation burns using local bone marrow-derived stem cell administrations</article-title><source><italic>Wound Repair and Regeneration</italic></source><year>2010</year><volume>18</volume><issue>1</issue><fpage>50</fpage><lpage>58</lpage><pub-id pub-id-type="pmid">20082681</pub-id></element-citation></ref><ref id="B25"><label>25</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Becker</surname><given-names>W</given-names></name><name><surname>Meller</surname><given-names>J</given-names></name></person-group><article-title>The role of nuclear medicine in infection and inflammation</article-title><source><italic>The Lancet Infectious Diseases</italic></source><year>2001</year><volume>1</volume><issue>5</issue><fpage>326</fpage><lpage>333</lpage><pub-id pub-id-type="pmid">11871805</pub-id></element-citation></ref><ref id="B26"><label>26</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Blocklet</surname><given-names>D</given-names></name><name><surname>Toungouz</surname><given-names>M</given-names></name><name><surname>Kiss</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>111In-oxine and 99mTc-HMPAO labelling of antigen-loaded dendritic cells: in vivo imaging and influence on motility and actin content</article-title><source><italic>European Journal of Nuclear Medicine and Molecular Imaging</italic></source><year>2003</year><volume>30</volume><issue>3</issue><fpage>440</fpage><lpage>447</lpage><pub-id pub-id-type="pmid">12722741</pub-id></element-citation></ref><ref id="B27"><label>27</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bohnen</surname><given-names>NI</given-names></name><name><surname>Charron</surname><given-names>M</given-names></name><name><surname>Reyes</surname><given-names>J</given-names></name><etal></etal></person-group><article-title>Use of indium-111-labeled hepatocytes to determine the biodistribution of transplanted hepatocytes through portal vein infusion</article-title><source><italic>Clinical Nuclear Medicine</italic></source><year>2000</year><volume>25</volume><issue>6</issue><fpage>447</fpage><lpage>450</lpage><pub-id pub-id-type="pmid">10836694</pub-id></element-citation></ref><ref id="B28"><label>28</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Takemiya</surname><given-names>K</given-names></name><name><surname>Kai</surname><given-names>H</given-names></name><name><surname>Yasukawa</surname><given-names>H</given-names></name><name><surname>Tahara</surname><given-names>N</given-names></name><name><surname>Kato</surname><given-names>S</given-names></name><name><surname>Imaizumi</surname><given-names>T</given-names></name></person-group><article-title>Mesenchymal stem cell-based prostacyclin synthase gene therapy for pulmonary hypertension rats</article-title><source><italic>Basic Research in Cardiology</italic></source><year>2010</year><volume>105</volume><issue>3</issue><fpage>409</fpage><lpage>417</lpage><pub-id pub-id-type="pmid">19838762</pub-id></element-citation></ref><ref id="B29"><label>29</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kuyama</surname><given-names>J</given-names></name><name><surname>McCormack</surname><given-names>A</given-names></name><name><surname>George</surname><given-names>AJT</given-names></name><etal></etal></person-group><article-title>Indium-111 labelled lymphocytes: isotope distribution and cell division</article-title><source><italic>European Journal of Nuclear Medicine</italic></source><year>1997</year><volume>24</volume><issue>5</issue><fpage>488</fpage><lpage>496</lpage><pub-id pub-id-type="pmid">9142728</pub-id></element-citation></ref><ref id="B30"><label>30</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Marino</surname><given-names>R</given-names></name><name><surname>Martinez</surname><given-names>C</given-names></name><name><surname>Boyd</surname><given-names>K</given-names></name><name><surname>Dominici</surname><given-names>M</given-names></name><name><surname>Hofmann</surname><given-names>TJ</given-names></name><name><surname>Horwitz</surname><given-names>EM</given-names></name></person-group><article-title>Transplantable marrow osteoprogenitors engraft in discrete saturable sites in the marrow microenvironment</article-title><source><italic>Experimental Hematology</italic></source><year>2008</year><volume>36</volume><issue>3</issue><fpage>360</fpage><lpage>368</lpage><pub-id pub-id-type="pmid">18179857</pub-id></element-citation></ref><ref id="B31"><label>31</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Abdallah</surname><given-names>BM</given-names></name><name><surname>Kassem</surname><given-names>M</given-names></name></person-group><article-title>Human mesenchymal stem cells: from basic biology to clinical applications</article-title><source><italic>Gene Therapy</italic></source><year>2008</year><volume>15</volume><issue>2</issue><fpage>109</fpage><lpage>116</lpage><pub-id pub-id-type="pmid">17989700</pub-id></element-citation></ref><ref id="B32"><label>32</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Martin</surname><given-names>M</given-names></name><name><surname>Delanian</surname><given-names>S</given-names></name><name><surname>Sivan</surname><given-names>V</given-names></name><etal></etal></person-group><article-title>Radiation-induced superficial fibrosis and TGF-alpha 1</article-title><source><italic>Cancer/Radiothérapie</italic></source><year>2000</year><volume>4</volume><issue>5</issue><fpage>369</fpage><lpage>384</lpage></element-citation></ref><ref id="B33"><label>33</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Geris</surname><given-names>L</given-names></name><name><surname>Gerisch</surname><given-names>A</given-names></name><name><surname>Sloten</surname><given-names>JV</given-names></name><name><surname>Weiner</surname><given-names>R</given-names></name><name><surname>Oosterwyck</surname><given-names>HV</given-names></name></person-group><article-title>Angiogenesis in bone fracture healing: a bioregulatory model</article-title><source><italic>Journal of Theoretical Biology</italic></source><year>2008</year><volume>251</volume><issue>1</issue><fpage>137</fpage><lpage>158</lpage><pub-id pub-id-type="pmid">18155732</pub-id></element-citation></ref><ref id="B34"><label>34</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Phulpin</surname><given-names>B</given-names></name><name><surname>Gangloff</surname><given-names>P</given-names></name><name><surname>Tran</surname><given-names>N</given-names></name><name><surname>Bravetti</surname><given-names>P</given-names></name><name><surname>Merlin</surname><given-names>JL</given-names></name><name><surname>Dolivet</surname><given-names>G</given-names></name></person-group><article-title>Rehabilitation of irradiated head and neck tissues by autologous fat transplantation</article-title><source><italic>Plastic and Reconstructive Surgery</italic></source><year>2009</year><volume>123</volume><issue>4</issue><fpage>1187</fpage><lpage>1197</lpage><pub-id pub-id-type="pmid">19337087</pub-id></element-citation></ref><ref id="B35"><label>35</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mendonça</surname><given-names>JJ</given-names></name><name><surname>Juiz-Lopez</surname><given-names>P</given-names></name></person-group><article-title>Regenerative facial reconstruction of terminal stage osteoradionecrosis and other advanced craniofacial diseases with adult cultured stem and progenitor cells</article-title><source><italic>Plastic and Reconstructive Surgery</italic></source><year>2010</year><volume>126</volume><issue>5</issue><fpage>1699</fpage><lpage>1709</lpage><pub-id pub-id-type="pmid">21042127</pub-id></element-citation></ref><ref id="B36"><label>36</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Basciano</surname><given-names>L</given-names></name><name><surname>Nemos</surname><given-names>C</given-names></name><name><surname>Foliguet</surname><given-names>B</given-names></name><etal></etal></person-group><article-title>Long term culture of mesenchymal stem cells in hypoxia promotes a genetic program maintaining their undifferentiated and multipotent status</article-title><source><italic>BMC Cell Biology</italic></source><year>2011</year><volume>12, article 12</volume></element-citation></ref><ref id="B37"><label>37</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Holzwarth</surname><given-names>C</given-names></name><name><surname>Vaegler</surname><given-names>M</given-names></name><name><surname>Gieseke</surname><given-names>F</given-names></name><etal></etal></person-group><article-title>Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells</article-title><source><italic>BMC Cell Biology</italic></source><year>2010</year><volume>11, article 11</volume></element-citation></ref></ref-list></back><floats-group><fig id="fig1" position="float"><label>Figure 1</label><caption><p>Animal model of hindlimb irradiation. (a) Examples of pictures showing alopecia of the hindlimb 3 months after irradiation at a monodose of 30 Gy. (b) Examples of scintigraphic imaging showing the decrease of bone <sup>99m</sup>Tc-HDP on the irradiated hindlimb 3 months after irradiation.</p></caption><graphic xlink:href="JBB2011-560257.001"></graphic></fig><fig id="fig2" position="float"><label>Figure 2</label><caption><p>Mesenchymal quality of the engrafted BMSCs and injection procedure. (a) flow cytometry data depicting several conventional surface antigens of mesenchymal cells (CD34<monospace>−</monospace>, CD44+, CD45<monospace>−,</monospace> and CD90+) prior to implantation (passage 4). (b) technique of intramedullary injection (left panel) and on the right panel, the arrow indicates the bandage on the surgical site after BMSC engraftment.</p></caption><graphic xlink:href="JBB2011-560257.002"></graphic></fig><fig id="fig3" position="float"><label>Figure 3</label><caption><p>Example of scintigrams from <sup>111</sup>In/<sup>99m</sup>Tc dual-SPECT showing the short-term retention of <sup>111</sup>In-oxine-labeled BMSCs following intramedullary injection.</p></caption><graphic xlink:href="JBB2011-560257.003"></graphic></fig><fig id="fig4" position="float"><label>Figure 4</label><caption><p><italic>In vivo</italic> evolution of <sup>111</sup>In activity found in the tibia during the 7-day followup and estimation of the percentage of BMSCs retained within the injection site. Calculation of BMSCs retention in the tibia was defined as the ration of the mean radioactivity in the tibia to the mean radioactivity that remained in BMSCs at each time point.</p></caption><graphic xlink:href="JBB2011-560257.004"></graphic></fig><fig id="fig5" position="float"><label>Figure 5</label><caption><p>Two-month evolution of bone flood flow (a) and bone osteoblastic metabolism (b) in irradiated tibias treated with BMSCs (dark columns) and control (white columns), values being expressed as relative to baseline (% of uptake variations with regard to untreated hindlimb values). *<italic>P</italic> < 0.05 versus pretherapeutic data, <sup>†</sup><italic>P</italic> < 0.05 versus control group.</p></caption><graphic xlink:href="JBB2011-560257.005"></graphic></fig><table-wrap id="tab1" position="float"><label>Table 1</label><caption><p>Pretherapeutic value of <sup>99m</sup>Tc-HDP bone uptake of the rat hindlimbs. Results were expressed as percentage of total corporel activity.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1"></th><th align="center" rowspan="1" colspan="1"></th><th align="center" colspan="2" rowspan="1">Group 1</th><th align="center" colspan="2" rowspan="1">Group 2</th></tr><tr><th align="left" rowspan="1" colspan="1"></th><th align="center" rowspan="1" colspan="1"></th><th align="center" rowspan="1" colspan="1">Nonirradiated hindlimb</th><th align="center" rowspan="1" colspan="1">Irradiated hindlimb</th><th align="center" rowspan="1" colspan="1">Nonirradiated hindlimb</th><th align="center" rowspan="1" colspan="1">Irradiated hindlimb</th></tr></thead><tbody><tr><td align="left" rowspan="3" colspan="1">Bone blood flow</td><td align="center" rowspan="1" colspan="1">Knee</td><td align="center" rowspan="1" colspan="1">7.9 ± 1.0</td><td align="center" rowspan="1" colspan="1">8.3 ± 1.2</td><td align="center" rowspan="1" colspan="1">8.1 ± 1.3</td><td align="center" rowspan="1" colspan="1">8.3 ± 1.3</td></tr><tr><td align="center" rowspan="1" colspan="1">Tibia</td><td align="center" rowspan="1" colspan="1">3.82 ± 0.6</td><td align="center" rowspan="1" colspan="1">3.0 ± 0.8*</td><td align="center" rowspan="1" colspan="1">3.79 ± 1.0</td><td align="center" rowspan="1" colspan="1">3.2 ± 0.3*</td></tr><tr><td align="center" rowspan="1" colspan="1">Foot</td><td align="center" rowspan="1" colspan="1">2.4 ± 0.7</td><td align="center" rowspan="1" colspan="1">2.6 ± 0.8</td><td align="center" rowspan="1" colspan="1">2.7 ± 0.6</td><td align="center" rowspan="1" colspan="1">2.6 ± 0.7</td></tr><tr><td align="center" colspan="6" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="3" colspan="1">Bone osteoblastic metabolism</td><td align="center" rowspan="1" colspan="1">Knee</td><td align="center" rowspan="1" colspan="1">10.3 ± 3.0</td><td align="center" rowspan="1" colspan="1">9.9 ± 1.7</td><td align="center" rowspan="1" colspan="1">11.3 ± 4.9</td><td align="center" rowspan="1" colspan="1">8.9 ± 1.9</td></tr><tr><td align="center" rowspan="1" colspan="1">Tibia</td><td align="center" rowspan="1" colspan="1">2.2 ± 0.2</td><td align="center" rowspan="1" colspan="1">2.1 ± 0.1</td><td align="center" rowspan="1" colspan="1">2.3 ± 0.2</td><td align="center" rowspan="1" colspan="1">2.0 ± 0.3</td></tr><tr><td align="center" rowspan="1" colspan="1">Foot</td><td align="center" rowspan="1" colspan="1">3.8 ± 0.7</td><td align="center" rowspan="1" colspan="1">3.3 ± 1.0</td><td align="center" rowspan="1" colspan="1">3.7 ± 3.0</td><td align="center" rowspan="1" colspan="1">3.5 ± 1.4</td></tr></tbody></table><table-wrap-foot><fn><p>*<italic>P</italic> < 0.05 versus contralateral nonirradiated legs.</p></fn></table-wrap-foot></table-wrap><table-wrap id="tab2" position="float"><label>Table 2</label><caption><p>Post-therapeutic value of <sup>99m</sup>Tc-HDP bone uptake of the irradiated hindlimbs. Results were expressed as relative to the unirradiated hindlimb.</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1"></th><th align="center" rowspan="1" colspan="1"></th><th align="center" rowspan="1" colspan="1">Hindlimb</th><th align="center" rowspan="1" colspan="1">posttherapeutic 48 H</th><th align="center" rowspan="1" colspan="1">posttherapeutic 168 H</th><th align="center" rowspan="1" colspan="1">posttherapeutic 2 months</th></tr></thead><tbody><tr><td align="left" rowspan="6" colspan="1">Bone blood flow</td><td align="center" rowspan="2" colspan="1">Knee</td><td align="center" rowspan="1" colspan="1">Irradiated untreated</td><td align="center" rowspan="1" colspan="1">−0.40 ± 1.30</td><td align="center" rowspan="1" colspan="1">−0.76 ± 1.62</td><td align="center" rowspan="1" colspan="1">+0.16 ± 0.91</td></tr><tr><td align="center" rowspan="1" colspan="1">Irradiated treated</td><td align="center" rowspan="1" colspan="1">−0.30 ± 0.89</td><td align="center" rowspan="1" colspan="1">−1.18 ± 0.87</td><td align="center" rowspan="1" colspan="1">+0.20 ± 0.98</td></tr><tr><td align="center" rowspan="2" colspan="1">Tibia</td><td align="center" rowspan="1" colspan="1">Irradiated untreated</td><td align="center" rowspan="1" colspan="1">+0.95 ± 1.43</td><td align="center" rowspan="1" colspan="1">+0.21 ± 1.45</td><td align="center" rowspan="1" colspan="1">−0.01 ± 0.49</td></tr><tr><td align="center" rowspan="1" colspan="1">Irradiated treated</td><td align="center" rowspan="1" colspan="1">+2.00 ± 0.68*</td><td align="center" rowspan="1" colspan="1">+0.70 ± 1.03*</td><td align="center" rowspan="1" colspan="1">+0.40 ± 0.53</td></tr><tr><td align="center" rowspan="2" colspan="1">Foot</td><td align="center" rowspan="1" colspan="1">Irradiated untreated</td><td align="center" rowspan="1" colspan="1">+1.05 ± 1.12</td><td align="center" rowspan="1" colspan="1">+0.26 ± 1.57</td><td align="center" rowspan="1" colspan="1">+0.46 ± 0.31</td></tr><tr><td align="center" rowspan="1" colspan="1">Irradiated treated</td><td align="center" rowspan="1" colspan="1">+1.64 ± 1.25</td><td align="center" rowspan="1" colspan="1">+1.02 ± 0.96</td><td align="center" rowspan="1" colspan="1">+0.56 ± 0.90</td></tr><tr><td align="center" colspan="6" rowspan="1"><hr></hr></td></tr><tr><td align="left" rowspan="6" colspan="1">Bone osteoblastic metabolism</td><td align="center" rowspan="2" colspan="1">Knee</td><td align="center" rowspan="1" colspan="1">Irradiated untreated</td><td align="center" rowspan="1" colspan="1">−2.12 ± 1.25</td><td align="center" rowspan="1" colspan="1">−1.06 ± 1.06</td><td align="center" rowspan="1" colspan="1">−1.21 ± 1.13</td></tr><tr><td align="center" rowspan="1" colspan="1">Irradiated treated</td><td align="center" rowspan="1" colspan="1">−1.68 ± 1.43</td><td align="center" rowspan="1" colspan="1">−1.57 ± 1.44</td><td align="center" rowspan="1" colspan="1">−1.16 ± 0.98</td></tr><tr><td align="center" rowspan="2" colspan="1">Tibia</td><td align="center" rowspan="1" colspan="1">Irradiated untreated</td><td align="center" rowspan="1" colspan="1">+0.28 ± 0.85</td><td align="center" rowspan="1" colspan="1">−0.04 ± 0.67</td><td align="center" rowspan="1" colspan="1">−0.01 ± 0.66</td></tr><tr><td align="center" rowspan="1" colspan="1">Irradiated treated</td><td align="center" rowspan="1" colspan="1">+0.77 ± 0.56*</td><td align="center" rowspan="1" colspan="1">+0.47 ± 0.58*</td><td align="center" rowspan="1" colspan="1">+0.07 ± 0.56</td></tr><tr><td align="center" rowspan="2" colspan="1">Foot</td><td align="center" rowspan="1" colspan="1">Irradiated untreated</td><td align="center" rowspan="1" colspan="1">+0.36 ± 0.89</td><td align="center" rowspan="1" colspan="1">+0.01 ± 1.19</td><td align="center" rowspan="1" colspan="1">+0.07 ± 0.59</td></tr><tr><td align="center" rowspan="1" colspan="1">Irradiated treated</td><td align="center" rowspan="1" colspan="1">+1.07 ± 1.21</td><td align="center" rowspan="1" colspan="1">+0.58 ± 0.62</td><td align="center" rowspan="1" colspan="1">+0.43 ± 0.96</td></tr></tbody></table><table-wrap-foot><fn><p>*<italic>P</italic> < 0.05 versus contralateral nonirradiated legs.</p></fn></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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