Carr, CA;
Stuckey, DJ;
Tan, JJ;
Tan, SC;
Gomes, RSM;
Camelliti, P;
Messina, E;
... Clarke, K; + view all
(2011)
Cardiosphere-derived cells improve function in the infarcted rat heart for at least 16 weeks - an mri study.
PLoS ONE
, 6
(10)
10.1371/journal.pone.0025669.
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Abstract
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 (2×106) 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 (4×106) 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.
| Type: | Article |
|---|---|
| Title: | Cardiosphere-derived cells improve function in the infarcted rat heart for at least 16 weeks - an mri study |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0025669 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0025669 |
| Language: | English |
| Additional information: | © 2011 Carr et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by the British Heart Foundation (grant number PG/07/059/23259). Dr. Jun Tan and Dr. Suat Tan thank the Malaysian Ministry of Higher Education for studentships. Dr. Ellison is a recipient of a Marie Curie International Re-integration grant from the FP7 EU Marie Curie Actions (PIRG02-GA-2007-224853). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Imaging |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1386376 |
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