Abstract 3179: Cardiospheres Derived From Infarcted Myocardium Have the Potential for Myocardial Regeneration
Background: Cardiospheres (CSs) represent one type of cardiac stem cells. However, the availability of CSs from infarcted myocardium is unknown. We tested the hypothesis that acute myocardial infarction (MI) affects the generation of CSs in vitro, the CSs from injured heart have the potential for myocardial regeneration.
Methods: Adult C57BL mice were sacrificed at 1, 2 and 4 weeks post-MI. Sham-operated and non-operated mice were used as controls (n=6). CSs formed from the whole heart were quantified. CSs generated from various regions of heart 1-week post-MI were also quantified. The cell-components of CSs were analyzed by FACS and immunostaining. The CSs cells from 1-week post-MI heart of adult GFP transgenic mice were delivered into MI-hearts by echo-guided injection (2×105 cells/heart) (n=6). After 25 days, implanted cells were analyzed by immunohistochemical staining.
Results: The number of CSs from 1-week (354±50/heart) and 2-week (213±38/heart) post-MI hearts were higher than that from sham-operated (80±33/heart) and non-operated hearts (18±14/heart) (P<0.01). This increase was attenuated by 4-weeks post-MI (141±42/heart). In 1-week post-MI hearts, left ventricle, right ventricle, septum, left atrium and right atrium generated similar numbers of CSs per unit tissue (2.20 –3.8 CSs/mg, P=NS). In CSs from control hearts, 25.2±3.8% of cells were Sca1+/CD45−, 13.6±1.4% Nkx2.5+, 60.1±5.6% GATA4+ and 11.4±1.5% α-smooth muscle actin (SMA)+. The cell-types in CSs from MI-hearts were similar to those from control hearts, except CSs from 1-week post-MI hearts had more CD45+ (31.5±4.4%) and ckit+/CD45+ cells (5.5±2.3%) than those from control hearts (CD45+: 15.4±2.5%, ckit+/CD45+:1.3±0.3%, P<0.01). Implanted CSs cells from infarcted hearts differentiated into cardiomyocytes (Troponin I+), endothelial cell (CD31+) and smooth muscle cells (SMA+) in the infarct border zone 25 days post-injection.
Conclusions: CSs generation increases dramatically in 1 – 2 weeks post-MI hearts. Different cardiac regions generate similar numbers of CSs per unit tissue. CSs from MI-hearts can differentiate into cardiac cells in vivo. All of these suggest CSs can be isolated from any regions of heart at early stage post-MI, and be used for myocardial regeneration.