Restoration of Corneal Transparency by Mesenchymal Stem Cells
Identifieur interne : 000012 ( Pmc/Checkpoint ); précédent : 000011; suivant : 000013Restoration of Corneal Transparency by Mesenchymal Stem Cells
Auteurs : Sharad K. Mittal [États-Unis] ; Masahiro Omoto [États-Unis, Japon] ; Afsaneh Amouzegar [États-Unis] ; Anuradha Sahu [États-Unis] ; Alexandra Rezazadeh [États-Unis] ; Kishore R. Katikireddy [États-Unis] ; Dhvanit I. Shah [États-Unis] ; Srikant K. Sahu [États-Unis, Inde] ; Sunil K. Chauhan [États-Unis]Source :
- Stem Cell Reports [ 2213-6711 ] ; 2016.
Abstract
Transparency of the cornea is indispensable for optimal vision. Ocular trauma is a leading cause of corneal opacity, leading to 25 million cases of blindness annually. Recently, mesenchymal stem cells (MSCs) have gained prominence due to their inflammation-suppressing and tissue repair functions. Here, we investigate the potential of MSCs to restore corneal transparency following ocular injury. Using an in vivo mouse model of ocular injury, we report that MSCs have the capacity to restore corneal transparency by secreting high levels of hepatocyte growth factor (HGF). Interestingly, our data also show that HGF alone can restore corneal transparency, an observation that has translational implications for the development of HGF-based therapy.
Url:
DOI: 10.1016/j.stemcr.2016.09.001
PubMed: 27693426
PubMed Central: 5063582
Affiliations:
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Shah</name><affiliation wicri:level="1"><nlm:aff id="aff4">Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02114</wicri:regionArea><wicri:noRegion>MA 02114</wicri:noRegion></affiliation></author><author><name sortKey="Sahu, Srikant K" sort="Sahu, Srikant K" uniqKey="Sahu S" first="Srikant K." last="Sahu">Srikant K. Sahu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114</wicri:regionArea><wicri:noRegion>MA 02114</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">L.V. Prasad Eye Institute, Bhubaneswar, Odisha 751024, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>L.V. Prasad Eye Institute, Bhubaneswar, Odisha 751024</wicri:regionArea><wicri:noRegion>Odisha 751024</wicri:noRegion></affiliation></author><author><name sortKey="Chauhan, Sunil K" sort="Chauhan, Sunil K" uniqKey="Chauhan S" first="Sunil K." last="Chauhan">Sunil K. 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Mittal</name><affiliation wicri:level="1"><nlm:aff id="aff1">Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114</wicri:regionArea><wicri:noRegion>MA 02114</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology, Harvard Medical School, Boston, MA 02114</wicri:regionArea><wicri:noRegion>MA 02114</wicri:noRegion></affiliation></author><author><name sortKey="Omoto, Masahiro" sort="Omoto, Masahiro" uniqKey="Omoto M" first="Masahiro" last="Omoto">Masahiro Omoto</name><affiliation wicri:level="1"><nlm:aff id="aff1">Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114</wicri:regionArea><wicri:noRegion>MA 02114</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582</wicri:regionArea><placeName><settlement type="city">Tokyo</settlement><region type="région">Région de Kantō</region></placeName></affiliation></author><author><name sortKey="Amouzegar, Afsaneh" sort="Amouzegar, Afsaneh" uniqKey="Amouzegar A" first="Afsaneh" last="Amouzegar">Afsaneh Amouzegar</name><affiliation wicri:level="1"><nlm:aff id="aff1">Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114</wicri:regionArea><wicri:noRegion>MA 02114</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology, Harvard Medical School, Boston, MA 02114</wicri:regionArea><wicri:noRegion>MA 02114</wicri:noRegion></affiliation></author><author><name sortKey="Sahu, Anuradha" sort="Sahu, Anuradha" uniqKey="Sahu A" first="Anuradha" last="Sahu">Anuradha Sahu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114</wicri:regionArea><wicri:noRegion>MA 02114</wicri:noRegion></affiliation></author><author><name sortKey="Rezazadeh, Alexandra" sort="Rezazadeh, Alexandra" uniqKey="Rezazadeh A" first="Alexandra" last="Rezazadeh">Alexandra Rezazadeh</name><affiliation wicri:level="1"><nlm:aff id="aff1">Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114</wicri:regionArea><wicri:noRegion>MA 02114</wicri:noRegion></affiliation></author><author><name sortKey="Katikireddy, Kishore R" sort="Katikireddy, Kishore R" uniqKey="Katikireddy K" first="Kishore R." last="Katikireddy">Kishore R. Katikireddy</name><affiliation wicri:level="1"><nlm:aff id="aff1">Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114</wicri:regionArea><wicri:noRegion>MA 02114</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology, Harvard Medical School, Boston, MA 02114</wicri:regionArea><wicri:noRegion>MA 02114</wicri:noRegion></affiliation></author><author><name sortKey="Shah, Dhvanit I" sort="Shah, Dhvanit I" uniqKey="Shah D" first="Dhvanit I." last="Shah">Dhvanit I. Shah</name><affiliation wicri:level="1"><nlm:aff id="aff4">Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02114</wicri:regionArea><wicri:noRegion>MA 02114</wicri:noRegion></affiliation></author><author><name sortKey="Sahu, Srikant K" sort="Sahu, Srikant K" uniqKey="Sahu S" first="Srikant K." last="Sahu">Srikant K. Sahu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114</wicri:regionArea><wicri:noRegion>MA 02114</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">L.V. Prasad Eye Institute, Bhubaneswar, Odisha 751024, India</nlm:aff><country xml:lang="fr">Inde</country><wicri:regionArea>L.V. Prasad Eye Institute, Bhubaneswar, Odisha 751024</wicri:regionArea><wicri:noRegion>Odisha 751024</wicri:noRegion></affiliation></author><author><name sortKey="Chauhan, Sunil K" sort="Chauhan, Sunil K" uniqKey="Chauhan S" first="Sunil K." last="Chauhan">Sunil K. Chauhan</name><affiliation wicri:level="1"><nlm:aff id="aff1">Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114</wicri:regionArea><wicri:noRegion>MA 02114</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Ophthalmology, Harvard Medical School, Boston, MA 02114</wicri:regionArea><wicri:noRegion>MA 02114</wicri:noRegion></affiliation></author></analytic><series><title level="j">Stem Cell Reports</title><idno type="eISSN">2213-6711</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><p>Transparency of the cornea is indispensable for optimal vision. Ocular trauma is a leading cause of corneal opacity, leading to 25 million cases of blindness annually. Recently, mesenchymal stem cells (MSCs) have gained prominence due to their inflammation-suppressing and tissue repair functions. Here, we investigate the potential of MSCs to restore corneal transparency following ocular injury. Using an in vivo mouse model of ocular injury, we report that MSCs have the capacity to restore corneal transparency by secreting high levels of hepatocyte growth factor (HGF). Interestingly, our data also show that HGF alone can restore corneal transparency, an observation that has translational implications for the development of HGF-based therapy.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Abed, E" uniqKey="Abed E">E. Abed</name></author><author><name sortKey="Bouvard, B" uniqKey="Bouvard B">B. Bouvard</name></author><author><name sortKey="Martineau, X" uniqKey="Martineau X">X. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Stem Cell Reports</journal-id><journal-id journal-id-type="iso-abbrev">Stem Cell Reports</journal-id><journal-title-group><journal-title>Stem Cell Reports</journal-title></journal-title-group><issn pub-type="epub">2213-6711</issn><publisher><publisher-name>Elsevier</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27693426</article-id><article-id pub-id-type="pmc">5063582</article-id><article-id pub-id-type="publisher-id">S2213-6711(16)30187-4</article-id><article-id pub-id-type="doi">10.1016/j.stemcr.2016.09.001</article-id><article-categories><subj-group subj-group-type="heading"><subject>Report</subject></subj-group></article-categories><title-group><article-title>Restoration of Corneal Transparency by Mesenchymal Stem Cells</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Mittal</surname><given-names>Sharad K.</given-names></name><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff2" ref-type="aff">2</xref><xref rid="fn1" ref-type="fn">6</xref></contrib><contrib contrib-type="author"><name><surname>Omoto</surname><given-names>Masahiro</given-names></name><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff3" ref-type="aff">3</xref><xref rid="fn1" ref-type="fn">6</xref></contrib><contrib contrib-type="author"><name><surname>Amouzegar</surname><given-names>Afsaneh</given-names></name><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff2" ref-type="aff">2</xref></contrib><contrib contrib-type="author"><name><surname>Sahu</surname><given-names>Anuradha</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Rezazadeh</surname><given-names>Alexandra</given-names></name><xref rid="aff1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Katikireddy</surname><given-names>Kishore R.</given-names></name><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff2" ref-type="aff">2</xref></contrib><contrib contrib-type="author"><name><surname>Shah</surname><given-names>Dhvanit I.</given-names></name><xref rid="aff4" ref-type="aff">4</xref></contrib><contrib contrib-type="author"><name><surname>Sahu</surname><given-names>Srikant K.</given-names></name><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff5" ref-type="aff">5</xref></contrib><contrib contrib-type="author"><name><surname>Chauhan</surname><given-names>Sunil K.</given-names></name><email>sunil_chauhan@meei.harvard.edu</email><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff2" ref-type="aff">2</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Schepens Eye Research Institute, Massachusetts Eye and Ear, 20 Staniford Street, Boston, MA 02114, USA</aff><aff id="aff2"><label>2</label>Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA</aff><aff id="aff3"><label>3</label>Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan</aff><aff id="aff4"><label>4</label>Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02114, USA</aff><aff id="aff5"><label>5</label>L.V. Prasad Eye Institute, Bhubaneswar, Odisha 751024, India</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author <email>sunil_chauhan@meei.harvard.edu</email></corresp><fn id="fn1"><label>6</label><p id="ntpara0010">Co-first author</p></fn></author-notes><pub-date pub-type="pmc-release"><day>29</day><month>9</month><year>2016</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="collection"><day>11</day><month>10</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>29</day><month>9</month><year>2016</year></pub-date><volume>7</volume><issue>4</issue><fpage>583</fpage><lpage>590</lpage><history><date date-type="received"><day>31</day><month>5</month><year>2016</year></date><date date-type="rev-recd"><day>1</day><month>9</month><year>2016</year></date><date date-type="accepted"><day>2</day><month>9</month><year>2016</year></date></history><permissions><copyright-statement>© 2016 The Authors</copyright-statement><copyright-year>2016</copyright-year><license license-type="CC BY" xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).</license-p></license></permissions><abstract id="abs0010"><title>Summary</title><p>Transparency of the cornea is indispensable for optimal vision. Ocular trauma is a leading cause of corneal opacity, leading to 25 million cases of blindness annually. Recently, mesenchymal stem cells (MSCs) have gained prominence due to their inflammation-suppressing and tissue repair functions. Here, we investigate the potential of MSCs to restore corneal transparency following ocular injury. Using an in vivo mouse model of ocular injury, we report that MSCs have the capacity to restore corneal transparency by secreting high levels of hepatocyte growth factor (HGF). Interestingly, our data also show that HGF alone can restore corneal transparency, an observation that has translational implications for the development of HGF-based therapy.</p></abstract><abstract abstract-type="graphical" id="abs0015"><title>Graphical Abstract</title><fig id="undfig1" position="anchor"><graphic xlink:href="fx1"></graphic></fig></abstract><abstract abstract-type="author-highlights" id="abs0020"><title>Highlights</title><p><list list-type="simple"><list-item id="u0010"><label>•</label><p>Inflammation drives MSCs to secrete elevated levels of hepatocyte growth factor (HGF)</p></list-item><list-item id="u0015"><label>•</label><p>MSC-derived HGF restores corneal transparency by inhibiting myofibroblast generation</p></list-item><list-item id="u0020"><label>•</label><p>HGF alone can restore corneal transparency</p></list-item></list></p></abstract><abstract abstract-type="teaser" id="abs0025"><p>Ocular injury is a major cause of loss of corneal transparency, leading to blindness. Chauhan and colleagues’ data demonstrate that, following ocular injury, corneal transparency can be restored by MSCs, a process that is completely dependent upon HGF secretion by MSCs. Most importantly, they show that HGF alone can restore corneal transparency, a finding that offers a cell-free HGF-based therapeutic approach.</p></abstract></article-meta><notes><p id="misc0010">Published: September 29, 2016</p></notes></front><floats-group><fig id="fig1"><label>Figure 1</label><caption><p>MSCs Secrete High Levels of HGF upon Stimulation with IL-1β</p><p>(A) Schematic showing injury model of mouse cornea created by mechanical removal of epithelium and anterior stroma, and effect of mesenchymal stem cell (MSC) administration on corneal opacity.</p><p>(B) Micrographs showing MSC morphology in culture at second passage, and differentiation of MSCs into adipocytes. MSCs were cultured in adipogenic medium for 2 weeks and stained with oil red O dye; red-colored vacuoles (arrows) were observed within the cytoplasm, indicating their differentiation into adipocytes. Scale bar, 25 μm.</p><p>(C) Phenotypic characterization of in vitro expanded MSCs using flow cytometry confirmed their surface phenotype of CD45<sup>–</sup>CD34<sup>–</sup>SCA1<sup>+</sup>CD29<sup>+</sup>CD105<sup>+</sup> cells.</p><p>(D) MSCs were cultured in medium alone or with IL-1β for 24 hr. mRNA expression of indicated genes in MSCs were analyzed using real-time PCR.</p><p>(E) Protein expression of TGF-β1 and HGF was confirmed in culture supernatants of MSCs cultured in the presence or absence of IL-1β for 24 hr using ELISA. The values of mRNA and protein expression are shown as mean ± SD of three independent experiments.</p><p>(F and G) In vitro expanded MSCs were intravenously injected into the C57BL/6 mice 1 hr after corneal injury. Healthy corneas without injury were used as normal control. Corneas were harvested after 3 days, and (F) mRNA and (G) protein expressions of HGF were measured using real-time PCR and ELISA, respectively.</p><p>The values shown are mean ± SD and each corneal injury group consists of n = 6 mice. <sup>∗</sup>p < 0.003, <sup>∗∗</sup>p < 0.0001.</p></caption><graphic xlink:href="gr1"></graphic></fig><fig id="fig2"><label>Figure 2</label><caption><p>Restoration of Corneal Transparency Is Dependent upon HGF Expression by MSCs</p><p>(A) Schematic of experimental design.</p><p>(B) Real-time PCR analysis showing efficacy of <italic>Hgf</italic>-specific siRNA (siHGF) versus control siRNA (siCON) on downregulation of HGF expression in mesenchymal stem cells (MSCs). After corneal injury was induced in C57BL/6 mice, MSCs treated with control or <italic>Hgf</italic>-specific siRNA were intravenously administered 1 hr post injury and followed for 5 days. At days 1, 3, and 5 post injury, photographs of injured cornea with or without green fluorescein stain were captured using slit-lamp biomicroscopy. Corneal fluorescein staining was used to indicate epithelial defects and bright-field micrographs were used to evaluate corneal opacity.</p><p>(C and D) Representative bright-field microscopic images of injured cornea (C) were quantitated using Image J software to measure the corneal opacity scores (D).</p><p>(E) Representative biomicroscopic images showing green fluorescein-stained injured cornea.</p><p>(F) The fluorescein-stained area was quantitated using ImageJ software. A smaller area of fluorescein staining represents faster repair of corneal injury.</p><p>(G and H) At day 5 post injury, corneas were harvested. Total RNA was isolated from harvested corneas, and real-time PCR was performed to analyze mRNA expression of (G) <italic>α-Sma</italic> and (H) <italic>Tgf-β1</italic>.</p><p>The values shown are mean ± SD and each corneal injury group consists of n = 6 mice. <sup>∗</sup>p < 0.02, <sup>∗∗</sup>p < 0.005.</p></caption><graphic xlink:href="gr2"></graphic></fig><fig id="fig3"><label>Figure 3</label><caption><p>HGF Alone Is Sufficient to Inhibit Corneal Opacity and Inflammation</p><p>(A and B) A corneal fibroblast cell line (MK/T1) was stimulated with TGF-β1 in the presence or absence of HGF for 24 hr. α-SMA expression was assessed (A) at mRNA level using real-time PCR and (B) at protein level by immunohistochemistry. The values shown are the mean ± SD of three independent experiments.</p><p>(C–K) Corneal injury was induced by mechanical removal of corneal epithelium and anterior stroma in C57BL/6 mice. Thereafter, 5 μL of 0.1% murine recombinant HGF in PBS per eye was applied topically to the injured eye twice a day up to 7 days after injury. A control group received a similar dosage of mouse serum albumin. At days 1, 3, 5, and 7 post injury, bright-field photographs of injured corneas were captured to evaluate corneal opacity using slit-lamp biomicroscopy. Representative bright-field images of injured corneas (C) were quantitated using Image J software to assess corneal opacity scores (D). Corneas were harvested at 7 days post injury. Cross-sections were stained with H&E to visualize corneal tissue structure and infiltration of inflammatory cells (E), and measure corneal tissue thickness (F). For immunocytochemistry analysis (G), cross-sections were immunostained with the fibrosis marker α-SMA (green). In addition, harvested corneas were analyzed for their mRNA expression of (H) <italic>α-Sma</italic>, (I) <italic>Tgf-β1</italic>, (J) <italic>Il-1β</italic>, and (K) <italic>Tnf-α</italic> using real-time PCR.</p><p>The values shown are mean ± SD and each corneal injury group consists of n = 6 mice. <sup>∗</sup>p < 0.01, <sup>∗∗</sup>p < 0.005. Scale bars, 50 μm.</p></caption><graphic xlink:href="gr3"></graphic></fig></floats-group></pmc><affiliations><list><country><li>Inde</li><li>Japon</li><li>États-Unis</li></country><region><li>Région de Kantō</li></region><settlement><li>Tokyo</li></settlement></list><tree><country name="États-Unis"><noRegion><name sortKey="Mittal, Sharad K" sort="Mittal, Sharad K" uniqKey="Mittal S" first="Sharad K." last="Mittal">Sharad K. Mittal</name></noRegion><name sortKey="Amouzegar, Afsaneh" sort="Amouzegar, Afsaneh" uniqKey="Amouzegar A" first="Afsaneh" last="Amouzegar">Afsaneh Amouzegar</name><name sortKey="Amouzegar, Afsaneh" sort="Amouzegar, Afsaneh" uniqKey="Amouzegar A" first="Afsaneh" last="Amouzegar">Afsaneh Amouzegar</name><name sortKey="Chauhan, Sunil K" sort="Chauhan, Sunil K" uniqKey="Chauhan S" first="Sunil K." last="Chauhan">Sunil K. Chauhan</name><name sortKey="Chauhan, Sunil K" sort="Chauhan, Sunil K" uniqKey="Chauhan S" first="Sunil K." last="Chauhan">Sunil K. Chauhan</name><name sortKey="Katikireddy, Kishore R" sort="Katikireddy, Kishore R" uniqKey="Katikireddy K" first="Kishore R." last="Katikireddy">Kishore R. Katikireddy</name><name sortKey="Katikireddy, Kishore R" sort="Katikireddy, Kishore R" uniqKey="Katikireddy K" first="Kishore R." last="Katikireddy">Kishore R. Katikireddy</name><name sortKey="Mittal, Sharad K" sort="Mittal, Sharad K" uniqKey="Mittal S" first="Sharad K." last="Mittal">Sharad K. Mittal</name><name sortKey="Omoto, Masahiro" sort="Omoto, Masahiro" uniqKey="Omoto M" first="Masahiro" last="Omoto">Masahiro Omoto</name><name sortKey="Rezazadeh, Alexandra" sort="Rezazadeh, Alexandra" uniqKey="Rezazadeh A" first="Alexandra" last="Rezazadeh">Alexandra Rezazadeh</name><name sortKey="Sahu, Anuradha" sort="Sahu, Anuradha" uniqKey="Sahu A" first="Anuradha" last="Sahu">Anuradha Sahu</name><name sortKey="Sahu, Srikant K" sort="Sahu, Srikant K" uniqKey="Sahu S" first="Srikant K." last="Sahu">Srikant K. Sahu</name><name sortKey="Shah, Dhvanit I" sort="Shah, Dhvanit I" uniqKey="Shah D" first="Dhvanit I." last="Shah">Dhvanit I. Shah</name></country><country name="Japon"><region name="Région de Kantō"><name sortKey="Omoto, Masahiro" sort="Omoto, Masahiro" uniqKey="Omoto M" first="Masahiro" last="Omoto">Masahiro Omoto</name></region></country><country name="Inde"><noRegion><name sortKey="Sahu, Srikant K" sort="Sahu, Srikant K" uniqKey="Sahu S" first="Srikant K." last="Sahu">Srikant K. Sahu</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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