title: Cardiosphere-derived cells improve function in the infarcted rat heart for at least 16 weeks--an MRI study.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: Department of Physiology, University of Oxford, Oxford, United Kingdom. Carolyn.Carr@dpag.ox.ac.uk
authors: Carolyn A
authors: CA
authors: Carr
authors: Daniel J
authors: DJ
authors: Stuckey
authors: Jun Jie
authors: JJ
authors: Tan
authors: Suat Cheng
authors: SC
authors: Tan
authors: Renata S M
authors: RS
authors: Gomes
authors: Patrizia
authors: P
authors: Camelliti
authors: Elisa
authors: E
authors: Messina
authors: Alessandro
authors: A
authors: Giacomello
authors: Georgina M
authors: GM
authors: Ellison
authors: Kieran
authors: K
authors: Clarke
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D005290:Ferric Compounds; D049452:Green Fluorescent Proteins; D006334:Heart Function Tests; D019028:Magnetic Resonance Imaging, Cine; D032386:Myoblasts, Cardiac / Q000637:transplantation*; D009203:Myocardial Infarction / Q000628:therapy*; D051381:Rats; D033581:Stem Cell Transplantation / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005290:Ferric Compounds; D049452:Green Fluorescent Proteins; C000499:ferric oxide