260 - A comparison of single donor cardiac-derived stem cells

Abstract

Over the past decade, several adult cardiac-derived cell products have been investigated as a means of directly replacing injured myocardium, but the relative utility of various cell types remain unclear. In this study, a direct head-to-head comparison of cardiac c-Kit+ cells, cardiosphere-derived cells (CDCs) and explant-derived cardiac stem cells (EDCs) cultured from the same human myocardial biopsy using in vitro assays for clonogenic self-renewal and multipotency was conducted using cell-type specific published culture methods. While c-Kit-/CD90+/CD105+ and c-Kit-/CD90-/CD105+ single cell clones derived from either CDCs or EDCs demonstrated clonogenic self-renewal and multipotent differentiation, c-Kit+ clones isolated directly from heart biopsies or from expanded CDCs or EDCs exhibited low cloning efficiency (≈1.5% vs. 8–15% seen with other CDC/EDC sub-populations, p = ns for c-Kit+ cell source) and premature growth arrest after 2 weeks of culture. Inductive culture of expanded cells “ready” for therapeutic delivery promoted the adoption of cardiac lineages with flow cytometry demonstrating EDCs being more apt to adopt a cardiomyocyte (38 ± 2% vs. 18 ± 1% or 10 ± 1% in CDCs (p = 0.001) or c-Kit+ cells (p = 0.0003)) or smooth muscle lineage (9 ± 1% vs. 7 ± 1% or 2 ± 1% in CDCs (p = 0.04) or c-Kit+ cells (p = 0.0005)). Finally, overexpression of cardiomyogenic microRNA-1 boosted adoption of a cardiac fate with less differentiation seen in treated c-Kit + cells. In conclusion, CDCs and EDCs possess the greatest ability to adopt a cardiomyocyte lineage, rationalizing attempts to promote long-term engraftment with the promise of directly replacing lost myocardium.