Cardiosphere-derived cells improve function in the infarcted rat heart for at least 16 weeks--an MRI study.
AIMS: Endogenous cardiac progenitor cells, expanded from explants via cardiosphere formation, present a promising cell source to prevent heart failure following myocardial infarction. Here we used cine-magnetic resonance imaging (MRI) to track administered cardiosphere-derived cells (CDCs) and to me...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Public Library of Science
2011
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| _version_ | 1826293508402577408 |
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| author | Carr, C Stuckey, D Tan, J Tan, S Gomes, R Camelliti, P Messina, E Giacomello, A Ellison, G Clarke, K |
| author_facet | Carr, C Stuckey, D Tan, J Tan, S Gomes, R Camelliti, P Messina, E Giacomello, A Ellison, G Clarke, K |
| author_sort | Carr, C |
| collection | OXFORD |
| description | AIMS: Endogenous cardiac progenitor cells, expanded from explants via cardiosphere formation, present a promising cell source to prevent heart failure following myocardial infarction. Here we used cine-magnetic resonance imaging (MRI) to track administered cardiosphere-derived cells (CDCs) and to measure changes in cardiac function over four months in the infarcted rat heart. METHODS AND RESULTS: CDCs, cultured from neonatal rat heart, comprised a heterogeneous population including cells expressing the mesenchymal markers CD90 and CD105, the stem cell marker c-kit and the pluripotency markers Sox2, Oct3/4 and Klf-4. CDCs (2 × 10(6)) expressing green fluorescent protein (GFP+) were labelled with fluorescent micron-sized particles of iron oxide (MPIO). Labelled cells were administered to the infarcted rat hearts (n = 7) by intramyocardial injection immediately following reperfusion, then by systemic infusion (4 × 10(6)) 2 days later. A control group (n = 7) was administered cell medium. MR hypointensities caused by the MPIOs were detected at all times and GFP+ cells containing MPIO particles were identified in tissue slices at 16 weeks. At two days after infarction, cardiac function was similar between groups. By 6 weeks, ejection fractions in control hearts had significantly decreased (47 ± 2%), but this was not evident in CDC-treated hearts (56 ± 3%). The significantly higher ejection fractions in the CDC-treated group were maintained for a further 10 weeks. In addition, CDC-treated rat hearts had significantly increased capillary density in the peri-infarct region and lower infarct sizes. MPIO-labelled cells also expressed cardiac troponin I, von Willebrand factor and smooth muscle actin, suggesting their differentiation along the cardiomyocyte lineage and the formation of new blood vessels. CONCLUSIONS: CDCs were retained in the infarcted rat heart for 16 weeks and improved cardiac function. |
| first_indexed | 2024-03-07T03:31:12Z |
| format | Journal article |
| id | oxford-uuid:bac5e5f0-f8c5-4569-9ef8-53ada3f93818 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:31:12Z |
| publishDate | 2011 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:bac5e5f0-f8c5-4569-9ef8-53ada3f938182022-03-27T05:12:13ZCardiosphere-derived cells improve function in the infarcted rat heart for at least 16 weeks--an MRI study.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bac5e5f0-f8c5-4569-9ef8-53ada3f93818EnglishSymplectic Elements at OxfordPublic Library of Science2011Carr, CStuckey, DTan, JTan, SGomes, RCamelliti, PMessina, EGiacomello, AEllison, GClarke, KAIMS: Endogenous cardiac progenitor cells, expanded from explants via cardiosphere formation, present a promising cell source to prevent heart failure following myocardial infarction. Here we used cine-magnetic resonance imaging (MRI) to track administered cardiosphere-derived cells (CDCs) and to measure changes in cardiac function over four months in the infarcted rat heart. METHODS AND RESULTS: CDCs, cultured from neonatal rat heart, comprised a heterogeneous population including cells expressing the mesenchymal markers CD90 and CD105, the stem cell marker c-kit and the pluripotency markers Sox2, Oct3/4 and Klf-4. CDCs (2 × 10(6)) expressing green fluorescent protein (GFP+) were labelled with fluorescent micron-sized particles of iron oxide (MPIO). Labelled cells were administered to the infarcted rat hearts (n = 7) by intramyocardial injection immediately following reperfusion, then by systemic infusion (4 × 10(6)) 2 days later. A control group (n = 7) was administered cell medium. MR hypointensities caused by the MPIOs were detected at all times and GFP+ cells containing MPIO particles were identified in tissue slices at 16 weeks. At two days after infarction, cardiac function was similar between groups. By 6 weeks, ejection fractions in control hearts had significantly decreased (47 ± 2%), but this was not evident in CDC-treated hearts (56 ± 3%). The significantly higher ejection fractions in the CDC-treated group were maintained for a further 10 weeks. In addition, CDC-treated rat hearts had significantly increased capillary density in the peri-infarct region and lower infarct sizes. MPIO-labelled cells also expressed cardiac troponin I, von Willebrand factor and smooth muscle actin, suggesting their differentiation along the cardiomyocyte lineage and the formation of new blood vessels. CONCLUSIONS: CDCs were retained in the infarcted rat heart for 16 weeks and improved cardiac function. |
| spellingShingle | Carr, C Stuckey, D Tan, J Tan, S Gomes, R Camelliti, P Messina, E Giacomello, A Ellison, G Clarke, K Cardiosphere-derived cells improve function in the infarcted rat heart for at least 16 weeks--an MRI study. |
| title | Cardiosphere-derived cells improve function in the infarcted rat heart for at least 16 weeks--an MRI study. |
| title_full | Cardiosphere-derived cells improve function in the infarcted rat heart for at least 16 weeks--an MRI study. |
| title_fullStr | Cardiosphere-derived cells improve function in the infarcted rat heart for at least 16 weeks--an MRI study. |
| title_full_unstemmed | Cardiosphere-derived cells improve function in the infarcted rat heart for at least 16 weeks--an MRI study. |
| title_short | Cardiosphere-derived cells improve function in the infarcted rat heart for at least 16 weeks--an MRI study. |
| title_sort | cardiosphere derived cells improve function in the infarcted rat heart for at least 16 weeks an mri study |
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