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Transplantation of cardiac-committed mouse embryonic stem cells to infarcted sheep myocardium: a preclinical study
Heart failure develops after myocardial infarction and is a major cause of morbidity and mortality. The ability to direct differentiation of embryonic stem cells (ESC) towards a cardiomyogenic phenotype makes them an attractive therapeutic option for cardiac repair, but species-specific and individu...
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Published in: | The Lancet (British edition) 2005-09, Vol.366 (9490), p.1005-1012 |
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creator | Ménard, Claudine Hagège, Albert A Agbulut, Onnik Barro, Marietta Morichetti, Miguel Cortes Brasselet, Camille Bel, Alain Messas, Emmanuel Bissery, Alvine Bruneval, Patrick Desnos, Michel Pucéat, Michel Menasché, Philippe |
description | Heart failure develops after myocardial infarction and is a major cause of morbidity and mortality. The ability to direct differentiation of embryonic stem cells (ESC) towards a cardiomyogenic phenotype makes them an attractive therapeutic option for cardiac repair, but species-specific and individual-specific immunological imprinting remains a hurdle. Our aim was to ascertain whether the purported immune privilege of ESC allows for their cross-species engraftment in a clinically relevant large-animal model.
We studied engraftment and differentiation of cardiac-committed mouse ESC in 18 sheep in which a myocardial infarction had been induced; nine controls received medium and nine sheep (five of which were immunosuppressed) received ESC. The gain in myocardial function was measured by echocardiography 1 month after cell transplantation.
Cardiac-committed murine ESC engrafted in infarcted myocardium of immunosuppressed and immunocompetent sheep, and differentiated into mature cardiomyocytes that expressed connexins. Colonisation of the scar area by ESC was accompanied by a functional benefit of the damaged myocardium. Left-ventricular ejection fraction deteriorated in the control group by a median of 9·9% (range −20 to 0·3) relative to baseline (p=0·011) whereas in the treated group it improved by 6·6% (−5·7 to 50·8; comparison between groups p=0·002).
These findings obtained in a clinically relevant large-animal model of heart failure strengthen the potential therapeutic use of ESC to regenerate the severely dysfunctional myocardium and bring additional evidence for an immune privilege of these cells. |
doi_str_mv | 10.1016/S0140-6736(05)67380-1 |
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We studied engraftment and differentiation of cardiac-committed mouse ESC in 18 sheep in which a myocardial infarction had been induced; nine controls received medium and nine sheep (five of which were immunosuppressed) received ESC. The gain in myocardial function was measured by echocardiography 1 month after cell transplantation.
Cardiac-committed murine ESC engrafted in infarcted myocardium of immunosuppressed and immunocompetent sheep, and differentiated into mature cardiomyocytes that expressed connexins. Colonisation of the scar area by ESC was accompanied by a functional benefit of the damaged myocardium. Left-ventricular ejection fraction deteriorated in the control group by a median of 9·9% (range −20 to 0·3) relative to baseline (p=0·011) whereas in the treated group it improved by 6·6% (−5·7 to 50·8; comparison between groups p=0·002).
These findings obtained in a clinically relevant large-animal model of heart failure strengthen the potential therapeutic use of ESC to regenerate the severely dysfunctional myocardium and bring additional evidence for an immune privilege of these cells.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(05)67380-1</identifier><identifier>PMID: 16168783</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>London: Elsevier Ltd</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animal models ; Animals ; Applied cell therapy and gene therapy ; Biological and medical sciences ; Cardiology. Vascular system ; Cell Differentiation ; Cell Division ; Cell Lineage ; Coronary heart disease ; Embryo, Mammalian - cytology ; General aspects ; Graft Survival ; Growth factors ; Heart ; Heart failure ; Leukemia ; Medical sciences ; Mice ; Myocardial infarction ; Myocardial Infarction - physiopathology ; Myocardial Infarction - therapy ; Myocardium - cytology ; Myocardium - metabolism ; Rodents ; Sheep ; Stem Cell Transplantation ; Stem cells ; Stroke Volume ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Transplants & implants ; Tumors</subject><ispartof>The Lancet (British edition), 2005-09, Vol.366 (9490), p.1005-1012</ispartof><rights>2005 Elsevier Ltd</rights><rights>2005 INIST-CNRS</rights><rights>Copyright Lancet Ltd. Sep 17-Sep 23, 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-a7ea0d7e24ebb1f646c4451542979f721dace8f3317021a7a3bba089ad93f67f3</citedby><cites>FETCH-LOGICAL-c455t-a7ea0d7e24ebb1f646c4451542979f721dace8f3317021a7a3bba089ad93f67f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17102385$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16168783$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ménard, Claudine</creatorcontrib><creatorcontrib>Hagège, Albert A</creatorcontrib><creatorcontrib>Agbulut, Onnik</creatorcontrib><creatorcontrib>Barro, Marietta</creatorcontrib><creatorcontrib>Morichetti, Miguel Cortes</creatorcontrib><creatorcontrib>Brasselet, Camille</creatorcontrib><creatorcontrib>Bel, Alain</creatorcontrib><creatorcontrib>Messas, Emmanuel</creatorcontrib><creatorcontrib>Bissery, Alvine</creatorcontrib><creatorcontrib>Bruneval, Patrick</creatorcontrib><creatorcontrib>Desnos, Michel</creatorcontrib><creatorcontrib>Pucéat, Michel</creatorcontrib><creatorcontrib>Menasché, Philippe</creatorcontrib><title>Transplantation of cardiac-committed mouse embryonic stem cells to infarcted sheep myocardium: a preclinical study</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>Heart failure develops after myocardial infarction and is a major cause of morbidity and mortality. The ability to direct differentiation of embryonic stem cells (ESC) towards a cardiomyogenic phenotype makes them an attractive therapeutic option for cardiac repair, but species-specific and individual-specific immunological imprinting remains a hurdle. Our aim was to ascertain whether the purported immune privilege of ESC allows for their cross-species engraftment in a clinically relevant large-animal model.
We studied engraftment and differentiation of cardiac-committed mouse ESC in 18 sheep in which a myocardial infarction had been induced; nine controls received medium and nine sheep (five of which were immunosuppressed) received ESC. The gain in myocardial function was measured by echocardiography 1 month after cell transplantation.
Cardiac-committed murine ESC engrafted in infarcted myocardium of immunosuppressed and immunocompetent sheep, and differentiated into mature cardiomyocytes that expressed connexins. Colonisation of the scar area by ESC was accompanied by a functional benefit of the damaged myocardium. Left-ventricular ejection fraction deteriorated in the control group by a median of 9·9% (range −20 to 0·3) relative to baseline (p=0·011) whereas in the treated group it improved by 6·6% (−5·7 to 50·8; comparison between groups p=0·002).
These findings obtained in a clinically relevant large-animal model of heart failure strengthen the potential therapeutic use of ESC to regenerate the severely dysfunctional myocardium and bring additional evidence for an immune privilege of these cells.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animal models</subject><subject>Animals</subject><subject>Applied cell therapy and gene therapy</subject><subject>Biological and medical sciences</subject><subject>Cardiology. Vascular system</subject><subject>Cell Differentiation</subject><subject>Cell Division</subject><subject>Cell Lineage</subject><subject>Coronary heart disease</subject><subject>Embryo, Mammalian - cytology</subject><subject>General aspects</subject><subject>Graft Survival</subject><subject>Growth factors</subject><subject>Heart</subject><subject>Heart failure</subject><subject>Leukemia</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Myocardial infarction</subject><subject>Myocardial Infarction - physiopathology</subject><subject>Myocardial Infarction - therapy</subject><subject>Myocardium - cytology</subject><subject>Myocardium - metabolism</subject><subject>Rodents</subject><subject>Sheep</subject><subject>Stem Cell Transplantation</subject><subject>Stem cells</subject><subject>Stroke Volume</subject><subject>Transfusions. Complications. Transfusion reactions. 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The ability to direct differentiation of embryonic stem cells (ESC) towards a cardiomyogenic phenotype makes them an attractive therapeutic option for cardiac repair, but species-specific and individual-specific immunological imprinting remains a hurdle. Our aim was to ascertain whether the purported immune privilege of ESC allows for their cross-species engraftment in a clinically relevant large-animal model.
We studied engraftment and differentiation of cardiac-committed mouse ESC in 18 sheep in which a myocardial infarction had been induced; nine controls received medium and nine sheep (five of which were immunosuppressed) received ESC. The gain in myocardial function was measured by echocardiography 1 month after cell transplantation.
Cardiac-committed murine ESC engrafted in infarcted myocardium of immunosuppressed and immunocompetent sheep, and differentiated into mature cardiomyocytes that expressed connexins. Colonisation of the scar area by ESC was accompanied by a functional benefit of the damaged myocardium. Left-ventricular ejection fraction deteriorated in the control group by a median of 9·9% (range −20 to 0·3) relative to baseline (p=0·011) whereas in the treated group it improved by 6·6% (−5·7 to 50·8; comparison between groups p=0·002).
These findings obtained in a clinically relevant large-animal model of heart failure strengthen the potential therapeutic use of ESC to regenerate the severely dysfunctional myocardium and bring additional evidence for an immune privilege of these cells.</abstract><cop>London</cop><pub>Elsevier Ltd</pub><pmid>16168783</pmid><doi>10.1016/S0140-6736(05)67380-1</doi><tpages>8</tpages></addata></record> |
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subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animal models Animals Applied cell therapy and gene therapy Biological and medical sciences Cardiology. Vascular system Cell Differentiation Cell Division Cell Lineage Coronary heart disease Embryo, Mammalian - cytology General aspects Graft Survival Growth factors Heart Heart failure Leukemia Medical sciences Mice Myocardial infarction Myocardial Infarction - physiopathology Myocardial Infarction - therapy Myocardium - cytology Myocardium - metabolism Rodents Sheep Stem Cell Transplantation Stem cells Stroke Volume Transfusions. Complications. Transfusion reactions. Cell and gene therapy Transplants & implants Tumors |
title | Transplantation of cardiac-committed mouse embryonic stem cells to infarcted sheep myocardium: a preclinical study |
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