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Cardiosphere-Derived Cells Improve Function in the Infarcted Rat Heart for at Least 16 Weeks - an MRI Study

Carr, CA and Stuckey, DJ and Tan, JJ and Tan, SC and Gomes, RSM and Camelliti, P and Messina, E and Giacomello, A and Ellison, GM and Clarke, K (2011) Cardiosphere-Derived Cells Improve Function in the Infarcted Rat Heart for at Least 16 Weeks - an MRI Study. PLOS ONE, 6 (10). ISSN 1932-6203

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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 (26106) 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 (46106) 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 (4762%), but this was not evident in CDC-treated hearts (5663%). 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.

Item Type: Article
Uncontrolled Keywords: MD Multidisciplinary
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: PUBLIC LIBRARY SCIENCE
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Date Deposited: 28 Jul 2016 10:04
Last Modified: 28 Jul 2016 10:04
DOI or Identification number: 10.1371/journal.pone.0025669
URI: http://researchonline.ljmu.ac.uk/id/eprint/3956

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