Hepatic cell sheets engineered from human mesenchymal stem cells with a single small molecule compound IC-2 ameliorate acute liver injury in mice.
Identifieur interne : 000253 ( Main/Exploration ); précédent : 000252; suivant : 000254Hepatic cell sheets engineered from human mesenchymal stem cells with a single small molecule compound IC-2 ameliorate acute liver injury in mice.
Auteurs : Noriko Itaba [Japon] ; Ikuya Noda [Japon] ; Hiroyuki Oka [Japon] ; Yohei Kono [Japon] ; Kaori Okinaka [Japon] ; Tsuyoshi Yokobata [Japon] ; Shizuma Okazaki [Japon] ; Minoru Morimoto [Japon] ; Goshi Shiota [Japon]Source :
- Regenerative therapy [ 2352-3204 ] ; 2018.
Abstract
Introduction
We previously reported that transplantation of hepatic cell sheets from human bone marrow-derived mesenchymal stem cells (BM-MSCs) with hexachlorophene, a Wnt/β-catenin signaling inhibitor, ameliorated acute liver injury. In a further previous report, we identified IC-2, a newly synthesized derivative of the Wnt/β-catenin signaling inhibitor ICG-001, as a potent inducer of hepatic differentiation of BM-MSCs.
Methods
We manufactured hepatic cell sheets by engineering from human BM-MSCs using the single small molecule IC-2. The therapeutic potential of IC-2-induced hepatic cell sheets was assessed by transplantation of IC-2- and hexachlorophene-treated hepatic cell sheets using a mouse model of acute liver injury.
Results
Significant improvement of liver injury was elicited by the IC-2-treated hepatic cell sheets. The expression of complement C3 was enhanced by IC-2, followed by prominent hepatocyte proliferation stimulated through the activation of NF-κB and its downstream molecule STAT-3. Indeed, IC-2 also enhanced the expression of amphiregulin, resulting in the activation of the EGFR pathway and further stimulation of hepatocyte proliferation. As another important therapeutic mechanism, we revealed prominent reduction of oxidative stress mediated through upregulation of the thioredoxin (TRX) system by IC-2-treated hepatic cell sheets. The effects mediated by IC-2-treated sheets were superior compared with those mediated by hexachlorophene-treated sheets.
Conclusion
The single compound IC-2 induced hepatic cell sheets that possess potent regeneration capacity and ameliorate acute liver injury.
DOI: 10.1016/j.reth.2018.07.001
PubMed: 30525075
PubMed Central: PMC6222293
Affiliations:
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Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503</wicri:regionArea><wicri:noRegion>Tottori 683-8503</wicri:noRegion></affiliation></author><author><name sortKey="Morimoto, Minoru" sort="Morimoto, Minoru" uniqKey="Morimoto M" first="Minoru" last="Morimoto">Minoru Morimoto</name><affiliation wicri:level="1"><nlm:affiliation>Research Initiative Center, Tottori University, 4-101 Koyama, Tottori 680-8550, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Research Initiative Center, Tottori University, 4-101 Koyama, Tottori 680-8550</wicri:regionArea><wicri:noRegion>Tottori 680-8550</wicri:noRegion></affiliation></author><author><name sortKey="Shiota, Goshi" sort="Shiota, Goshi" uniqKey="Shiota G" first="Goshi" last="Shiota">Goshi Shiota</name><affiliation wicri:level="1"><nlm:affiliation>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503</wicri:regionArea><wicri:noRegion>Tottori 683-8503</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2018">2018</date><idno type="RBID">pubmed:30525075</idno><idno type="pmid">30525075</idno><idno type="doi">10.1016/j.reth.2018.07.001</idno><idno type="pmc">PMC6222293</idno><idno type="wicri:Area/Main/Corpus">000185</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000185</idno><idno type="wicri:Area/Main/Curation">000185</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000185</idno><idno type="wicri:Area/Main/Exploration">000185</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Hepatic cell sheets engineered from human mesenchymal stem cells with a single small molecule compound IC-2 ameliorate acute liver injury in mice.</title><author><name sortKey="Itaba, Noriko" sort="Itaba, Noriko" uniqKey="Itaba N" first="Noriko" last="Itaba">Noriko Itaba</name><affiliation wicri:level="1"><nlm:affiliation>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503</wicri:regionArea><wicri:noRegion>Tottori 683-8503</wicri:noRegion></affiliation></author><author><name sortKey="Noda, Ikuya" sort="Noda, Ikuya" uniqKey="Noda I" first="Ikuya" last="Noda">Ikuya Noda</name><affiliation wicri:level="1"><nlm:affiliation>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503</wicri:regionArea><wicri:noRegion>Tottori 683-8503</wicri:noRegion></affiliation></author><author><name sortKey="Oka, Hiroyuki" sort="Oka, Hiroyuki" uniqKey="Oka H" first="Hiroyuki" last="Oka">Hiroyuki Oka</name><affiliation wicri:level="1"><nlm:affiliation>Research Initiative Center, Tottori University, 4-101 Koyama, Tottori 680-8550, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Research Initiative Center, Tottori University, 4-101 Koyama, Tottori 680-8550</wicri:regionArea><wicri:noRegion>Tottori 680-8550</wicri:noRegion></affiliation></author><author><name sortKey="Kono, Yohei" sort="Kono, Yohei" uniqKey="Kono Y" first="Yohei" last="Kono">Yohei Kono</name><affiliation wicri:level="1"><nlm:affiliation>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503</wicri:regionArea><wicri:noRegion>Tottori 683-8503</wicri:noRegion></affiliation></author><author><name sortKey="Okinaka, Kaori" sort="Okinaka, Kaori" uniqKey="Okinaka K" first="Kaori" last="Okinaka">Kaori Okinaka</name><affiliation wicri:level="1"><nlm:affiliation>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503</wicri:regionArea><wicri:noRegion>Tottori 683-8503</wicri:noRegion></affiliation></author><author><name sortKey="Yokobata, Tsuyoshi" sort="Yokobata, Tsuyoshi" uniqKey="Yokobata T" first="Tsuyoshi" last="Yokobata">Tsuyoshi Yokobata</name><affiliation wicri:level="1"><nlm:affiliation>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503</wicri:regionArea><wicri:noRegion>Tottori 683-8503</wicri:noRegion></affiliation></author><author><name sortKey="Okazaki, Shizuma" sort="Okazaki, Shizuma" uniqKey="Okazaki S" first="Shizuma" last="Okazaki">Shizuma Okazaki</name><affiliation wicri:level="1"><nlm:affiliation>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503</wicri:regionArea><wicri:noRegion>Tottori 683-8503</wicri:noRegion></affiliation></author><author><name sortKey="Morimoto, Minoru" sort="Morimoto, Minoru" uniqKey="Morimoto M" first="Minoru" last="Morimoto">Minoru Morimoto</name><affiliation wicri:level="1"><nlm:affiliation>Research Initiative Center, Tottori University, 4-101 Koyama, Tottori 680-8550, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Research Initiative Center, Tottori University, 4-101 Koyama, Tottori 680-8550</wicri:regionArea><wicri:noRegion>Tottori 680-8550</wicri:noRegion></affiliation></author><author><name sortKey="Shiota, Goshi" sort="Shiota, Goshi" uniqKey="Shiota G" first="Goshi" last="Shiota">Goshi Shiota</name><affiliation wicri:level="1"><nlm:affiliation>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503</wicri:regionArea><wicri:noRegion>Tottori 683-8503</wicri:noRegion></affiliation></author></analytic><series><title level="j">Regenerative therapy</title><idno type="eISSN">2352-3204</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>Introduction</b></p><p>We previously reported that transplantation of hepatic cell sheets from human bone marrow-derived mesenchymal stem cells (BM-MSCs) with hexachlorophene, a Wnt/β-catenin signaling inhibitor, ameliorated acute liver injury. In a further previous report, we identified IC-2, a newly synthesized derivative of the Wnt/β-catenin signaling inhibitor ICG-001, as a potent inducer of hepatic differentiation of BM-MSCs.</p></div><div type="abstract" xml:lang="en"><p><b>Methods</b></p><p>We manufactured hepatic cell sheets by engineering from human BM-MSCs using the single small molecule IC-2. The therapeutic potential of IC-2-induced hepatic cell sheets was assessed by transplantation of IC-2- and hexachlorophene-treated hepatic cell sheets using a mouse model of acute liver injury.</p></div><div type="abstract" xml:lang="en"><p><b>Results</b></p><p>Significant improvement of liver injury was elicited by the IC-2-treated hepatic cell sheets. The expression of complement C3 was enhanced by IC-2, followed by prominent hepatocyte proliferation stimulated through the activation of NF-κB and its downstream molecule STAT-3. Indeed, IC-2 also enhanced the expression of amphiregulin, resulting in the activation of the EGFR pathway and further stimulation of hepatocyte proliferation. As another important therapeutic mechanism, we revealed prominent reduction of oxidative stress mediated through upregulation of the thioredoxin (TRX) system by IC-2-treated hepatic cell sheets. The effects mediated by IC-2-treated sheets were superior compared with those mediated by hexachlorophene-treated sheets.</p></div><div type="abstract" xml:lang="en"><p><b>Conclusion</b></p><p>The single compound IC-2 induced hepatic cell sheets that possess potent regeneration capacity and ameliorate acute liver injury.</p></div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">30525075</PMID><DateRevised><Year>2020</Year><Month>10</Month><Day>01</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">2352-3204</ISSN><JournalIssue CitedMedium="Internet"><Volume>9</Volume><PubDate><Year>2018</Year><Month>Dec</Month></PubDate></JournalIssue><Title>Regenerative therapy</Title><ISOAbbreviation>Regen Ther</ISOAbbreviation></Journal><ArticleTitle>Hepatic cell sheets engineered from human mesenchymal stem cells with a single small molecule compound IC-2 ameliorate acute liver injury in mice.</ArticleTitle><Pagination><MedlinePgn>45-57</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.reth.2018.07.001</ELocationID><Abstract><AbstractText Label="Introduction" NlmCategory="UNASSIGNED">We previously reported that transplantation of hepatic cell sheets from human bone marrow-derived mesenchymal stem cells (BM-MSCs) with hexachlorophene, a Wnt/β-catenin signaling inhibitor, ameliorated acute liver injury. In a further previous report, we identified IC-2, a newly synthesized derivative of the Wnt/β-catenin signaling inhibitor ICG-001, as a potent inducer of hepatic differentiation of BM-MSCs.</AbstractText><AbstractText Label="Methods" NlmCategory="UNASSIGNED">We manufactured hepatic cell sheets by engineering from human BM-MSCs using the single small molecule IC-2. The therapeutic potential of IC-2-induced hepatic cell sheets was assessed by transplantation of IC-2- and hexachlorophene-treated hepatic cell sheets using a mouse model of acute liver injury.</AbstractText><AbstractText Label="Results" NlmCategory="UNASSIGNED">Significant improvement of liver injury was elicited by the IC-2-treated hepatic cell sheets. The expression of complement C3 was enhanced by IC-2, followed by prominent hepatocyte proliferation stimulated through the activation of NF-κB and its downstream molecule STAT-3. Indeed, IC-2 also enhanced the expression of amphiregulin, resulting in the activation of the EGFR pathway and further stimulation of hepatocyte proliferation. As another important therapeutic mechanism, we revealed prominent reduction of oxidative stress mediated through upregulation of the thioredoxin (TRX) system by IC-2-treated hepatic cell sheets. The effects mediated by IC-2-treated sheets were superior compared with those mediated by hexachlorophene-treated sheets.</AbstractText><AbstractText Label="Conclusion" NlmCategory="UNASSIGNED">The single compound IC-2 induced hepatic cell sheets that possess potent regeneration capacity and ameliorate acute liver injury.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Itaba</LastName><ForeName>Noriko</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Noda</LastName><ForeName>Ikuya</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oka</LastName><ForeName>Hiroyuki</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Research Initiative Center, Tottori University, 4-101 Koyama, Tottori 680-8550, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kono</LastName><ForeName>Yohei</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Okinaka</LastName><ForeName>Kaori</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yokobata</LastName><ForeName>Tsuyoshi</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Okazaki</LastName><ForeName>Shizuma</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Morimoto</LastName><ForeName>Minoru</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Research Initiative Center, Tottori University, 4-101 Koyama, Tottori 680-8550, Japan.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shiota</LastName><ForeName>Goshi</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>08</Month><Day>24</Day></ArticleDate></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Regen Ther</MedlineTA><NlmUniqueID>101709085</NlmUniqueID><ISSNLinking>2352-3204</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">8-OHdG, 8-hydroxydeoxyguanosine</Keyword><Keyword MajorTopicYN="N">A1AT, α1-antitrypsin</Keyword><Keyword MajorTopicYN="N">ALT, alanine aminotransferase</Keyword><Keyword MajorTopicYN="N">APOE, apolipoprotein E</Keyword><Keyword MajorTopicYN="N">AREG, amphiregulin</Keyword><Keyword MajorTopicYN="N">AST, aspartate aminotransferase</Keyword><Keyword MajorTopicYN="N">Acute liver failure</Keyword><Keyword MajorTopicYN="N">BM-MSCs, bone marrow-derived mesenchymal stem cells</Keyword><Keyword MajorTopicYN="N">C3, complement C3</Keyword><Keyword MajorTopicYN="N">C4A, complement C4A</Keyword><Keyword MajorTopicYN="N">C5aR, complement C5a receptor</Keyword><Keyword MajorTopicYN="N">CBP, CREB-binding protein</Keyword><Keyword MajorTopicYN="N">CCl4, carbon tetrachloride</Keyword><Keyword MajorTopicYN="N">CP, ceruloplasmin</Keyword><Keyword MajorTopicYN="N">ChREBP, Carbohydrate-responsive element-binding protein</Keyword><Keyword MajorTopicYN="N">ChoREs, carbohydrate response elements</Keyword><Keyword MajorTopicYN="N">DMSO, dimethyl sulfoxide</Keyword><Keyword MajorTopicYN="N">EGFR, epidermal growth factor receptor</Keyword><Keyword MajorTopicYN="N">ERK, extracellular signal-regulated kinase</Keyword><Keyword MajorTopicYN="N">GPX, glutathione peroxidase</Keyword><Keyword MajorTopicYN="N">GR, Glutathione reductase</Keyword><Keyword MajorTopicYN="N">GRX, glutaredoxin</Keyword><Keyword MajorTopicYN="N">GSH, glutathione</Keyword><Keyword MajorTopicYN="N">HB-EGF, heparin binding-epidermal growth factor-like growth factor</Keyword><Keyword MajorTopicYN="N">HGFR, hepatocyte growth factor receptor</Keyword><Keyword MajorTopicYN="N">Hepatic cell sheets</Keyword><Keyword MajorTopicYN="N">IL-1ra, interleukin-1 receptor antagonist</Keyword><Keyword MajorTopicYN="N">IL-6, interleukin-6</Keyword><Keyword MajorTopicYN="N">LXR, liver X receptor</Keyword><Keyword MajorTopicYN="N">Liver regeneration</Keyword><Keyword MajorTopicYN="N">MDA, malondialdehyde</Keyword><Keyword MajorTopicYN="N">Mesenchymal stem cells</Keyword><Keyword MajorTopicYN="N">NF-κB, nuclear factor-kappa B</Keyword><Keyword MajorTopicYN="N">PCNA, proliferating cell nuclear antigen</Keyword><Keyword MajorTopicYN="N">PRX, peroxiredoxin</Keyword><Keyword MajorTopicYN="N">RBP4, retinol binding protein 4</Keyword><Keyword MajorTopicYN="N">SOD, superoxide dismutase</Keyword><Keyword MajorTopicYN="N">STAT-3, Signal Tranducer and Activator of Transcription 3</Keyword><Keyword MajorTopicYN="N">TF, transferrin</Keyword><Keyword MajorTopicYN="N">TGFα, transforming growth factor alpha</Keyword><Keyword MajorTopicYN="N">TNFα, tumor necrosis factor alpha</Keyword><Keyword MajorTopicYN="N">TRX, thioredoxin</Keyword><Keyword MajorTopicYN="N">TRXR, thioredoxin reductase</Keyword><Keyword MajorTopicYN="N">Wnt/β-catenin signal inhibitor</Keyword><Keyword MajorTopicYN="N">hGAPDH, human glyceraldehyde 3-phosphate dehydrogenase</Keyword><Keyword MajorTopicYN="N">mActb, mouse actin, beta</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>05</Month><Day>09</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2018</Year><Month>06</Month><Day>22</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018</Year><Month>07</Month><Day>02</Day></PubMedPubDate><PubMedPubDate 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Noda</name><name sortKey="Oka, Hiroyuki" sort="Oka, Hiroyuki" uniqKey="Oka H" first="Hiroyuki" last="Oka">Hiroyuki Oka</name><name sortKey="Okazaki, Shizuma" sort="Okazaki, Shizuma" uniqKey="Okazaki S" first="Shizuma" last="Okazaki">Shizuma Okazaki</name><name sortKey="Okinaka, Kaori" sort="Okinaka, Kaori" uniqKey="Okinaka K" first="Kaori" last="Okinaka">Kaori Okinaka</name><name sortKey="Shiota, Goshi" sort="Shiota, Goshi" uniqKey="Shiota G" first="Goshi" last="Shiota">Goshi Shiota</name><name sortKey="Yokobata, Tsuyoshi" sort="Yokobata, Tsuyoshi" uniqKey="Yokobata T" first="Tsuyoshi" last="Yokobata">Tsuyoshi Yokobata</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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