Choice of cell-delivery route for skeletal myoblast transplantation for treating post-infarction chronic heart failure in rat.
<h4>Background</h4>Intramyocardial injection of skeletal myoblasts (SMB) has been shown to be a promising strategy for treating post-infarction chronic heart failure. However, insufficient therapeutic benefit and occurrence of ventricular arrhythmias are concerns. We hypothesised that th...
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Public Library of Science (PLoS)
2008-08-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0003071&type=printable |
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| author | Satsuki Fukushima Steven R Coppen Joon Lee Kenichi Yamahara Leanne E Felkin Cesare M N Terracciano Paul J R Barton Magdi H Yacoub Ken Suzuki |
| author_facet | Satsuki Fukushima Steven R Coppen Joon Lee Kenichi Yamahara Leanne E Felkin Cesare M N Terracciano Paul J R Barton Magdi H Yacoub Ken Suzuki |
| author_sort | Satsuki Fukushima |
| collection | DOAJ |
| description | <h4>Background</h4>Intramyocardial injection of skeletal myoblasts (SMB) has been shown to be a promising strategy for treating post-infarction chronic heart failure. However, insufficient therapeutic benefit and occurrence of ventricular arrhythmias are concerns. We hypothesised that the use of a retrograde intracoronary route for SMB-delivery might favourably alter the behaviour of the grafted SMB, consequently modulating the therapeutic effects and arrhythmogenicity.<h4>Methods and results</h4>Three weeks after coronary artery ligation in female wild-type rats, 5x10(6) GFP-expressing SMB or PBS only (control) were injected via either the intramyocardial or retrograde intracoronary routes. Injection of SMB via either route similarly improved cardiac performance and physical activity, associated with reduced cardiomyocyte-hypertrophy and fibrosis. Grafted SMB via either route were only present in low numbers in the myocardium, analysed by real-time PCR for the Y-chromosome specific gene, Sry. Cardiomyogenic differentiation of grafted SMB was extremely rare. Continuous ECG monitoring by telemetry revealed that only intramyocardial injection of SMB produced spontaneous ventricular tachycardia up to 14 days, associated with local myocardial heterogeneity generated by clusters of injected SMB and accumulated inflammatory cells. A small number of ventricular premature contractions with latent ventricular tachycardia were detected in the late-phase of SMB injection regardless of the injection-route.<h4>Conclusion</h4>Retrograde intracoronary injection of SMB provided significant therapeutic benefits with attenuated early-phase arrhythmogenicity in treating ischaemic cardiomyopathy, indicating the promising utility of this route for SMB-delivery. Late-phase arrhythmogenicity remains a concern, regardless of the delivery route. |
| format | Article |
| id | doaj-art-2e84452c26fe4d078bff17eba1cc42c4 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2008-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-2e84452c26fe4d078bff17eba1cc42c42025-08-20T02:17:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-08-0138e307110.1371/journal.pone.0003071Choice of cell-delivery route for skeletal myoblast transplantation for treating post-infarction chronic heart failure in rat.Satsuki FukushimaSteven R CoppenJoon LeeKenichi YamaharaLeanne E FelkinCesare M N TerraccianoPaul J R BartonMagdi H YacoubKen Suzuki<h4>Background</h4>Intramyocardial injection of skeletal myoblasts (SMB) has been shown to be a promising strategy for treating post-infarction chronic heart failure. However, insufficient therapeutic benefit and occurrence of ventricular arrhythmias are concerns. We hypothesised that the use of a retrograde intracoronary route for SMB-delivery might favourably alter the behaviour of the grafted SMB, consequently modulating the therapeutic effects and arrhythmogenicity.<h4>Methods and results</h4>Three weeks after coronary artery ligation in female wild-type rats, 5x10(6) GFP-expressing SMB or PBS only (control) were injected via either the intramyocardial or retrograde intracoronary routes. Injection of SMB via either route similarly improved cardiac performance and physical activity, associated with reduced cardiomyocyte-hypertrophy and fibrosis. Grafted SMB via either route were only present in low numbers in the myocardium, analysed by real-time PCR for the Y-chromosome specific gene, Sry. Cardiomyogenic differentiation of grafted SMB was extremely rare. Continuous ECG monitoring by telemetry revealed that only intramyocardial injection of SMB produced spontaneous ventricular tachycardia up to 14 days, associated with local myocardial heterogeneity generated by clusters of injected SMB and accumulated inflammatory cells. A small number of ventricular premature contractions with latent ventricular tachycardia were detected in the late-phase of SMB injection regardless of the injection-route.<h4>Conclusion</h4>Retrograde intracoronary injection of SMB provided significant therapeutic benefits with attenuated early-phase arrhythmogenicity in treating ischaemic cardiomyopathy, indicating the promising utility of this route for SMB-delivery. Late-phase arrhythmogenicity remains a concern, regardless of the delivery route.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0003071&type=printable |
| spellingShingle | Satsuki Fukushima Steven R Coppen Joon Lee Kenichi Yamahara Leanne E Felkin Cesare M N Terracciano Paul J R Barton Magdi H Yacoub Ken Suzuki Choice of cell-delivery route for skeletal myoblast transplantation for treating post-infarction chronic heart failure in rat. PLoS ONE |
| title | Choice of cell-delivery route for skeletal myoblast transplantation for treating post-infarction chronic heart failure in rat. |
| title_full | Choice of cell-delivery route for skeletal myoblast transplantation for treating post-infarction chronic heart failure in rat. |
| title_fullStr | Choice of cell-delivery route for skeletal myoblast transplantation for treating post-infarction chronic heart failure in rat. |
| title_full_unstemmed | Choice of cell-delivery route for skeletal myoblast transplantation for treating post-infarction chronic heart failure in rat. |
| title_short | Choice of cell-delivery route for skeletal myoblast transplantation for treating post-infarction chronic heart failure in rat. |
| title_sort | choice of cell delivery route for skeletal myoblast transplantation for treating post infarction chronic heart failure in rat |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0003071&type=printable |
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