Feasibility of Treating Irradiated Bone with Intramedullary Delivered Autologous Mesenchymal Stem Cells
Identifieur interne : 002F64 ( Pmc/Checkpoint ); précédent : 002F63; suivant : 002F65Feasibility of Treating Irradiated Bone with Intramedullary Delivered Autologous Mesenchymal Stem Cells
Auteurs : Bérengère Phulpin ; Gilles Dolivet ; Pierre-Yves Marie [France] ; Sylvain Poussier [France] ; Sandrine Huger [France] ; Pierre Bravetti [France] ; Pierre Graff [France] ; Jean-Louis Merlin [France] ; Nguyen TranSource :
- Journal of Biomedicine and Biotechnology [ 1110-7243 ] ; 2011.
Abstract
Url:
DOI: 10.1155/2011/560257
PubMed: 21941433
PubMed Central: 3163406
Affiliations:
Links toward previous steps (curation, corpus...)
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PMC:3163406Le document en format XML
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<affiliation><nlm:aff>NONE</nlm:aff>
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<author><name sortKey="Tran, Nguyen" sort="Tran, Nguyen" uniqKey="Tran N" first="Nguyen" last="Tran">Nguyen Tran</name>
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<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>
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<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>
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<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>
<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>
<affiliations><list><country><li>France</li>
</country>
<region><li>Grand Est</li>
<li>Lorraine (région)</li>
</region>
<settlement><li>Nancy</li>
<li>Vandoeuvre-lès- Nancy</li>
<li>Vandoeuvre-lès-Nancy</li>
</settlement>
</list>
<tree><noCountry><name sortKey="Dolivet, Gilles" sort="Dolivet, Gilles" uniqKey="Dolivet G" first="Gilles" last="Dolivet">Gilles Dolivet</name>
<name sortKey="Phulpin, Berengere" sort="Phulpin, Berengere" uniqKey="Phulpin B" first="Bérengère" last="Phulpin">Bérengère Phulpin</name>
<name sortKey="Tran, Nguyen" sort="Tran, Nguyen" uniqKey="Tran N" first="Nguyen" last="Tran">Nguyen Tran</name>
</noCountry>
<country name="France"><region name="Grand Est"><name sortKey="Marie, Pierre Yves" sort="Marie, Pierre Yves" uniqKey="Marie P" first="Pierre-Yves" last="Marie">Pierre-Yves Marie</name>
</region>
<name sortKey="Bravetti, Pierre" sort="Bravetti, Pierre" uniqKey="Bravetti P" first="Pierre" last="Bravetti">Pierre Bravetti</name>
<name sortKey="Graff, Pierre" sort="Graff, Pierre" uniqKey="Graff P" first="Pierre" last="Graff">Pierre Graff</name>
<name sortKey="Huger, Sandrine" sort="Huger, Sandrine" uniqKey="Huger S" first="Sandrine" last="Huger">Sandrine Huger</name>
<name sortKey="Merlin, Jean Louis" sort="Merlin, Jean Louis" uniqKey="Merlin J" first="Jean-Louis" last="Merlin">Jean-Louis Merlin</name>
<name sortKey="Poussier, Sylvain" sort="Poussier, Sylvain" uniqKey="Poussier S" first="Sylvain" last="Poussier">Sylvain Poussier</name>
</country>
</tree>
</affiliations>
</record>
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