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Increased predominance of the matured ventricular subtype in embryonic stem cell-derived cardiomyocytes in vivo
Accumulating evidence suggests that human pluripotent stem cell-derived cardiomyocytes can affect “heart regeneration”, replacing injured cardiac scar tissue with concomitant electrical integration. However, electrically coupled graft cardiomyocytes were found to innately induce transient post-trans...
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| Published in: | Scientific reports 2020-07, Vol.10 (1), p.11883-11883, Article 11883 |
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| creator | Ichimura, Hajime Kadota, Shin Kashihara, Toshihide Yamada, Mitsuhiko Ito, Kuniaki Kobayashi, Hideki Tanaka, Yuki Shiba, Naoko Chuma, Shinichiro Tohyama, Shugo Seto, Tatsuichiro Okada, Kenji Kuwahara, Koichiro Shiba, Yuji |
| description | Accumulating evidence suggests that human pluripotent stem cell-derived cardiomyocytes can affect “heart regeneration”, replacing injured cardiac scar tissue with concomitant electrical integration. However, electrically coupled graft cardiomyocytes were found to innately induce transient post-transplant ventricular tachycardia in recent large animal model transplantation studies. We hypothesised that these phenomena were derived from alterations in the grafted cardiomyocyte characteristics. In vitro experiments showed that human embryonic stem cell-derived cardiomyocytes (hESC-CMs) contain nodal-like cardiomyocytes that spontaneously contract faster than working-type cardiomyocytes. When transplanted into athymic rat hearts, proliferative capacity was lower for nodal-like than working-type cardiomyocytes with grafted cardiomyocytes eventually comprising only relatively matured ventricular cardiomyocytes. RNA-sequencing of engrafted hESC-CMs confirmed the increased expression of matured ventricular cardiomyocyte-related genes, and simultaneous decreased expression of nodal cardiomyocyte-related genes. Temporal engraftment of electrical excitable nodal-like cardiomyocytes may thus explain the transient incidence of post-transplant ventricular tachycardia, although further large animal model studies will be required to control post-transplant arrhythmia. |
| doi_str_mv | 10.1038/s41598-020-68373-9 |
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However, electrically coupled graft cardiomyocytes were found to innately induce transient post-transplant ventricular tachycardia in recent large animal model transplantation studies. We hypothesised that these phenomena were derived from alterations in the grafted cardiomyocyte characteristics. In vitro experiments showed that human embryonic stem cell-derived cardiomyocytes (hESC-CMs) contain nodal-like cardiomyocytes that spontaneously contract faster than working-type cardiomyocytes. When transplanted into athymic rat hearts, proliferative capacity was lower for nodal-like than working-type cardiomyocytes with grafted cardiomyocytes eventually comprising only relatively matured ventricular cardiomyocytes. RNA-sequencing of engrafted hESC-CMs confirmed the increased expression of matured ventricular cardiomyocyte-related genes, and simultaneous decreased expression of nodal cardiomyocyte-related genes. Temporal engraftment of electrical excitable nodal-like cardiomyocytes may thus explain the transient incidence of post-transplant ventricular tachycardia, although further large animal model studies will be required to control post-transplant arrhythmia.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-68373-9</identifier><identifier>PMID: 32681032</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/532/2117 ; 631/532/489 ; Action Potentials ; Animal models ; Arrhythmia ; Biomarkers ; Cardiac arrhythmia ; Cardiomyocytes ; Cell Differentiation ; Embryonic Stem Cells - cytology ; Embryonic Stem Cells - metabolism ; Engraftment ; Fluorescent Antibody Technique ; Gene Expression ; Gene Expression Profiling ; Heart Ventricles - cytology ; Heart Ventricles - metabolism ; Humanities and Social Sciences ; Immunohistochemistry ; multidisciplinary ; Myocytes, Cardiac - cytology ; Myocytes, Cardiac - metabolism ; Phylogeny ; Pluripotency ; Regeneration ; Ribonucleic acid ; RNA ; Science ; Science (multidisciplinary) ; Stem cells ; Tachycardia ; Transplants & implants ; Ventricle</subject><ispartof>Scientific reports, 2020-07, Vol.10 (1), p.11883-11883, Article 11883</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. 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Temporal engraftment of electrical excitable nodal-like cardiomyocytes may thus explain the transient incidence of post-transplant ventricular tachycardia, although further large animal model studies will be required to control post-transplant arrhythmia.</description><subject>631/532/2117</subject><subject>631/532/489</subject><subject>Action Potentials</subject><subject>Animal models</subject><subject>Arrhythmia</subject><subject>Biomarkers</subject><subject>Cardiac arrhythmia</subject><subject>Cardiomyocytes</subject><subject>Cell Differentiation</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Embryonic Stem Cells - metabolism</subject><subject>Engraftment</subject><subject>Fluorescent Antibody Technique</subject><subject>Gene Expression</subject><subject>Gene Expression Profiling</subject><subject>Heart Ventricles - cytology</subject><subject>Heart Ventricles - metabolism</subject><subject>Humanities and Social Sciences</subject><subject>Immunohistochemistry</subject><subject>multidisciplinary</subject><subject>Myocytes, Cardiac - 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Academic</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>Ichimura, Hajime</au><au>Kadota, Shin</au><au>Kashihara, Toshihide</au><au>Yamada, Mitsuhiko</au><au>Ito, Kuniaki</au><au>Kobayashi, Hideki</au><au>Tanaka, Yuki</au><au>Shiba, Naoko</au><au>Chuma, Shinichiro</au><au>Tohyama, Shugo</au><au>Seto, Tatsuichiro</au><au>Okada, Kenji</au><au>Kuwahara, Koichiro</au><au>Shiba, Yuji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased predominance of the matured ventricular subtype in embryonic stem cell-derived cardiomyocytes in vivo</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-07-17</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>11883</spage><epage>11883</epage><pages>11883-11883</pages><artnum>11883</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Accumulating evidence suggests that human pluripotent stem cell-derived cardiomyocytes can affect “heart regeneration”, replacing injured cardiac scar tissue with concomitant electrical integration. However, electrically coupled graft cardiomyocytes were found to innately induce transient post-transplant ventricular tachycardia in recent large animal model transplantation studies. We hypothesised that these phenomena were derived from alterations in the grafted cardiomyocyte characteristics. In vitro experiments showed that human embryonic stem cell-derived cardiomyocytes (hESC-CMs) contain nodal-like cardiomyocytes that spontaneously contract faster than working-type cardiomyocytes. When transplanted into athymic rat hearts, proliferative capacity was lower for nodal-like than working-type cardiomyocytes with grafted cardiomyocytes eventually comprising only relatively matured ventricular cardiomyocytes. RNA-sequencing of engrafted hESC-CMs confirmed the increased expression of matured ventricular cardiomyocyte-related genes, and simultaneous decreased expression of nodal cardiomyocyte-related genes. Temporal engraftment of electrical excitable nodal-like cardiomyocytes may thus explain the transient incidence of post-transplant ventricular tachycardia, although further large animal model studies will be required to control post-transplant arrhythmia.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32681032</pmid><doi>10.1038/s41598-020-68373-9</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-5898-3543</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 631/532/2117 631/532/489 Action Potentials Animal models Arrhythmia Biomarkers Cardiac arrhythmia Cardiomyocytes Cell Differentiation Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism Engraftment Fluorescent Antibody Technique Gene Expression Gene Expression Profiling Heart Ventricles - cytology Heart Ventricles - metabolism Humanities and Social Sciences Immunohistochemistry multidisciplinary Myocytes, Cardiac - cytology Myocytes, Cardiac - metabolism Phylogeny Pluripotency Regeneration Ribonucleic acid RNA Science Science (multidisciplinary) Stem cells Tachycardia Transplants & implants Ventricle |
| title | Increased predominance of the matured ventricular subtype in embryonic stem cell-derived cardiomyocytes in vivo |
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