Murine Cardiosphere-Derived Cells Are Impaired by Age but Not by Cardiac Dystrophic Dysfunction

Abstract

To be clinically relevant as a therapy for heart failure, endogenous progenitor cells must be isolated and expanded from aged and/or diseased tissue. Here, we investigated the effect of age and cardiac impairment resulting from lack of dystrophin on murine cardiosphere-derived cells (CDCs). CDCs were isolated and expanded from atrial biopsies from wild-type mice aged 1.5, 6, 18, and 24 months and from mdx mice aged 6 and 18 months. Cardiac function was measured in mdx mice and age-matched wild-type mice using highresolution cine magnetic resonance imaging. CDCs could be isolated and expanded from all mice, however, the number of cells obtained, and their regenerative potential, decreased with age, as demonstrated by decreased expression of stem cell markers, c-kit and Sca-1, and decreased cell proliferation, migration, clonogenicity, and differentiation. Six-month-old mdx mice showed right ventricular (RV) dilation and reduced RV ejection fraction (EF) in comparison to wild-type mice. Older mdx mice displayed significant RV and left ventricular dilation and decreased EF in both ventricles, compared with age-matched wild-type mice. Mdx mouse hearts contained significantly more fibrotic tissue than age-matched wild-type mouse hearts. However, CDCs isolated from mice aged 6 and 18 months had the same number and regenerative potential from mdx mice and agematched wild-type mice. Thus, the cardiac progenitor cell population is impaired by age but is not substantially altered by the progressive deterioration in function of the dystrophic heart.

Influence of aging on the quantity and quality of human cardiac stem cells

“…Several reports have demonstrated that c-kit positive cardiac stem cells from aged mice and patients underwent senescence 10 11 . CDCs from aged mice also have shown senescent phenotype and decreased cell proliferation, expression of stem cell markers and differentiation 12 . However, the influence of aging on cardiac stem cells is not fully understood.…”

Chronic High-Fat Feeding Affects the Mesenchymal Cell Population Expanded From Adipose Tissue but Not Cardiac Atria

“…No differences were noticed in the differentiation potential of CDCs from chow‐fed and HFD‐fed mice, that further confirms the conclusion that the high‐fat diet does not affect cardiac progenitor cells. In a recent study, we showed that CDCs isolated from mice aged 6 and 18 months had the same number and regenerative potential, whether from dystrophic mice, with mild cardiac impairment, or from age‐matched wild‐type mice [39]. The differentiation of ADMSCs increased expression levels of cardiac genes; however, ADMSCs from HFD‐fed mice seemed to have a slower response to the induction of differentiation.…”

Beyond cardiomyocyte loss: Role of Notch in cardiac aging

“…Likewise, senescent CPC, which have lost their telomerase activity because of aging, may give rise to structurally old cardiomyocytes destined to become less functional, with severely depressed mechanical performance and a marked tendency to apoptosis, along with the manifestation of an aging cardiac phenotype (Kajstura et al, ). Cardiosphere‐derived cells (CDC) isolated from aged mice showed a decline in the expression of CDC stem markers, such as c‐kit and Sca‐1, together with reduction of their clonogenic potential, suggesting failure of regenerative potential with age (Hsiao et al, ).…”