Teratocarcinomas Arising from Allogeneic Induced Pluripotent Stem Cell-Derived Cardiac Tissue Constructs Provoked Host Immune Rejection in Mice
Transplantation of induced pluripotent stem cell-derived cardiac tissue constructs is a promising regenerative treatment for cardiac failure: however, its tumourigenic potential is concerning. We hypothesised that the tumourigenic potential may be eliminated by the host immune response after allogen...
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| Veröffentlicht in: | Scientific reports 2016-01, Vol.6 (1), p.19464, Article 19464 |
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| creator | Kawamura, Ai Miyagawa, Shigeru Fukushima, Satsuki Kawamura, Takuji Kashiyama, Noriyuki Ito, Emiko Watabe, Tadashi Masuda, Shigeo Toda, Koichi Hatazawa, Jun Morii, Eiichi Sawa, Yoshiki |
| description | Transplantation of induced pluripotent stem cell-derived cardiac tissue constructs is a promising regenerative treatment for cardiac failure: however, its tumourigenic potential is concerning. We hypothesised that the tumourigenic potential may be eliminated by the host immune response after allogeneic cell transplantation. Scaffold-free iPSC-derived cardaic tissue sheets of C57BL/6 mouse origin were transplanted into the cardiac surface of syngeneic C57BL/6 mice and allogeneic BALB/c mice with or without tacrolimus injection. Syngeneic mice and tacrolimus-injected immunosuppressed allogeneic mice formed teratocarcinomas with identical phenotypes, characteristic and time courses, as assessed by imaging tools including
18
F-fluorodeoxyglucose-positron emission tomography. In contrast, temporarily immunosuppressed allogeneic mice, following cessation of tacrolimus injection displayed diminished progression of the teratocarcinoma, accompanied by an accumulation of CD4/CD8-positive T cells and finally achieved complete elimination of the teratocarcinoma. Our results indicated that malignant teratocarcinomas arising from induced pluripotent stem cell-derived cardiac tissue constructs provoked T cell-related host immune rejection to arrest tumour growth in murine allogeneic transplantation models. |
| doi_str_mv | 10.1038/srep19464 |
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18
F-fluorodeoxyglucose-positron emission tomography. In contrast, temporarily immunosuppressed allogeneic mice, following cessation of tacrolimus injection displayed diminished progression of the teratocarcinoma, accompanied by an accumulation of CD4/CD8-positive T cells and finally achieved complete elimination of the teratocarcinoma. Our results indicated that malignant teratocarcinomas arising from induced pluripotent stem cell-derived cardiac tissue constructs provoked T cell-related host immune rejection to arrest tumour growth in murine allogeneic transplantation models.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep19464</identifier><identifier>PMID: 26763872</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/100 ; 13/107 ; 13/109 ; 13/31 ; 13/51 ; 14/5 ; 14/63 ; 59/57 ; 59/78 ; 64/60 ; 692/308/2171 ; 692/4028/67/1679 ; 96/21 ; Animal models ; Animals ; Biopsy ; CD4 antigen ; CD8 antigen ; Cell Line ; Cell Transformation, Neoplastic ; Fluorodeoxyglucose F18 ; Gene Order ; Genetic Vectors - genetics ; Graft rejection ; Graft Rejection - immunology ; Heart diseases ; Heart transplantation ; Humanities and Social Sciences ; Immune response ; Immunocompromised Host ; Immunosuppressive Agents - administration & dosage ; Induced Pluripotent Stem Cells - cytology ; Induced Pluripotent Stem Cells - metabolism ; Injection ; Lymphocytes T ; Male ; Mice ; Mice, Transgenic ; Models, Animal ; multidisciplinary ; Myocytes, Cardiac - cytology ; Myocytes, Cardiac - pathology ; Pluripotency ; Positron emission tomography ; Science ; Stem Cell Transplantation - adverse effects ; Stem cells ; Syngeneic grafts ; T-Lymphocyte Subsets - immunology ; T-Lymphocyte Subsets - metabolism ; Tacrolimus ; Tacrolimus - administration & dosage ; Teratocarcinoma ; Teratocarcinoma - diagnosis ; Teratocarcinoma - etiology ; Teratocarcinoma - pathology ; Transplantation ; Transplantation, Homologous ; Tumors</subject><ispartof>Scientific reports, 2016-01, Vol.6 (1), p.19464, Article 19464</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Jan 2016</rights><rights>Copyright © 2016, Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c588t-c58b055562a957e02c382a5ec0e39a6dc5ef3154f9976363e99f93ceaffa827a3</citedby><cites>FETCH-LOGICAL-c588t-c58b055562a957e02c382a5ec0e39a6dc5ef3154f9976363e99f93ceaffa827a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725880/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725880/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,27907,27908,41103,42172,51559,53774,53776</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26763872$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kawamura, Ai</creatorcontrib><creatorcontrib>Miyagawa, Shigeru</creatorcontrib><creatorcontrib>Fukushima, Satsuki</creatorcontrib><creatorcontrib>Kawamura, Takuji</creatorcontrib><creatorcontrib>Kashiyama, Noriyuki</creatorcontrib><creatorcontrib>Ito, Emiko</creatorcontrib><creatorcontrib>Watabe, Tadashi</creatorcontrib><creatorcontrib>Masuda, Shigeo</creatorcontrib><creatorcontrib>Toda, Koichi</creatorcontrib><creatorcontrib>Hatazawa, Jun</creatorcontrib><creatorcontrib>Morii, Eiichi</creatorcontrib><creatorcontrib>Sawa, Yoshiki</creatorcontrib><title>Teratocarcinomas Arising from Allogeneic Induced Pluripotent Stem Cell-Derived Cardiac Tissue Constructs Provoked Host Immune Rejection in Mice</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Transplantation of induced pluripotent stem cell-derived cardiac tissue constructs is a promising regenerative treatment for cardiac failure: however, its tumourigenic potential is concerning. We hypothesised that the tumourigenic potential may be eliminated by the host immune response after allogeneic cell transplantation. Scaffold-free iPSC-derived cardaic tissue sheets of C57BL/6 mouse origin were transplanted into the cardiac surface of syngeneic C57BL/6 mice and allogeneic BALB/c mice with or without tacrolimus injection. Syngeneic mice and tacrolimus-injected immunosuppressed allogeneic mice formed teratocarcinomas with identical phenotypes, characteristic and time courses, as assessed by imaging tools including
18
F-fluorodeoxyglucose-positron emission tomography. In contrast, temporarily immunosuppressed allogeneic mice, following cessation of tacrolimus injection displayed diminished progression of the teratocarcinoma, accompanied by an accumulation of CD4/CD8-positive T cells and finally achieved complete elimination of the teratocarcinoma. Our results indicated that malignant teratocarcinomas arising from induced pluripotent stem cell-derived cardiac tissue constructs provoked T cell-related host immune rejection to arrest tumour growth in murine allogeneic transplantation models.</description><subject>13/100</subject><subject>13/107</subject><subject>13/109</subject><subject>13/31</subject><subject>13/51</subject><subject>14/5</subject><subject>14/63</subject><subject>59/57</subject><subject>59/78</subject><subject>64/60</subject><subject>692/308/2171</subject><subject>692/4028/67/1679</subject><subject>96/21</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biopsy</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Cell Line</subject><subject>Cell Transformation, Neoplastic</subject><subject>Fluorodeoxyglucose F18</subject><subject>Gene Order</subject><subject>Genetic Vectors - genetics</subject><subject>Graft rejection</subject><subject>Graft Rejection - immunology</subject><subject>Heart diseases</subject><subject>Heart transplantation</subject><subject>Humanities and Social Sciences</subject><subject>Immune response</subject><subject>Immunocompromised Host</subject><subject>Immunosuppressive Agents - 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administration & dosage</topic><topic>Teratocarcinoma</topic><topic>Teratocarcinoma - diagnosis</topic><topic>Teratocarcinoma - etiology</topic><topic>Teratocarcinoma - pathology</topic><topic>Transplantation</topic><topic>Transplantation, Homologous</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kawamura, Ai</creatorcontrib><creatorcontrib>Miyagawa, Shigeru</creatorcontrib><creatorcontrib>Fukushima, Satsuki</creatorcontrib><creatorcontrib>Kawamura, Takuji</creatorcontrib><creatorcontrib>Kashiyama, Noriyuki</creatorcontrib><creatorcontrib>Ito, Emiko</creatorcontrib><creatorcontrib>Watabe, Tadashi</creatorcontrib><creatorcontrib>Masuda, Shigeo</creatorcontrib><creatorcontrib>Toda, Koichi</creatorcontrib><creatorcontrib>Hatazawa, Jun</creatorcontrib><creatorcontrib>Morii, Eiichi</creatorcontrib><creatorcontrib>Sawa, Yoshiki</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kawamura, Ai</au><au>Miyagawa, Shigeru</au><au>Fukushima, Satsuki</au><au>Kawamura, Takuji</au><au>Kashiyama, Noriyuki</au><au>Ito, Emiko</au><au>Watabe, Tadashi</au><au>Masuda, Shigeo</au><au>Toda, Koichi</au><au>Hatazawa, Jun</au><au>Morii, Eiichi</au><au>Sawa, Yoshiki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Teratocarcinomas Arising from Allogeneic Induced Pluripotent Stem Cell-Derived Cardiac Tissue Constructs Provoked Host Immune Rejection in Mice</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-01-14</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>19464</spage><pages>19464-</pages><artnum>19464</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Transplantation of induced pluripotent stem cell-derived cardiac tissue constructs is a promising regenerative treatment for cardiac failure: however, its tumourigenic potential is concerning. We hypothesised that the tumourigenic potential may be eliminated by the host immune response after allogeneic cell transplantation. Scaffold-free iPSC-derived cardaic tissue sheets of C57BL/6 mouse origin were transplanted into the cardiac surface of syngeneic C57BL/6 mice and allogeneic BALB/c mice with or without tacrolimus injection. Syngeneic mice and tacrolimus-injected immunosuppressed allogeneic mice formed teratocarcinomas with identical phenotypes, characteristic and time courses, as assessed by imaging tools including
18
F-fluorodeoxyglucose-positron emission tomography. In contrast, temporarily immunosuppressed allogeneic mice, following cessation of tacrolimus injection displayed diminished progression of the teratocarcinoma, accompanied by an accumulation of CD4/CD8-positive T cells and finally achieved complete elimination of the teratocarcinoma. Our results indicated that malignant teratocarcinomas arising from induced pluripotent stem cell-derived cardiac tissue constructs provoked T cell-related host immune rejection to arrest tumour growth in murine allogeneic transplantation models.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26763872</pmid><doi>10.1038/srep19464</doi><oa>free_for_read</oa></addata></record> |
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| subjects | 13/100 13/107 13/109 13/31 13/51 14/5 14/63 59/57 59/78 64/60 692/308/2171 692/4028/67/1679 96/21 Animal models Animals Biopsy CD4 antigen CD8 antigen Cell Line Cell Transformation, Neoplastic Fluorodeoxyglucose F18 Gene Order Genetic Vectors - genetics Graft rejection Graft Rejection - immunology Heart diseases Heart transplantation Humanities and Social Sciences Immune response Immunocompromised Host Immunosuppressive Agents - administration & dosage Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - metabolism Injection Lymphocytes T Male Mice Mice, Transgenic Models, Animal multidisciplinary Myocytes, Cardiac - cytology Myocytes, Cardiac - pathology Pluripotency Positron emission tomography Science Stem Cell Transplantation - adverse effects Stem cells Syngeneic grafts T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism Tacrolimus Tacrolimus - administration & dosage Teratocarcinoma Teratocarcinoma - diagnosis Teratocarcinoma - etiology Teratocarcinoma - pathology Transplantation Transplantation, Homologous Tumors |
| title | Teratocarcinomas Arising from Allogeneic Induced Pluripotent Stem Cell-Derived Cardiac Tissue Constructs Provoked Host Immune Rejection in Mice |
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