Abstract 1015: Human Heart Contains A Stem Cell Population With Mesenchymal Properties

Abstract

Background Mesenchymal Stem Cells (MSC) were initially isolated from the bone marrow (BM) and identified as plastic adherent cells with a typical immunophenotype (negative for CD45, CD34, CD117 and HLA-DR and positive for CD105, CD90, CD44, CD73 and CD13), and able to differentiate into mesodermal lineages in vitro . Recently, MSC have been isolated from different adult tissues, i.e. liver, fat, kidney and thymus. Aim of the present study was to search for Cardiac Mesenchymal Stem Cells (C-MSC) in the adult human heart. Methods and Results : Auricle fragments were obtained from adult patients undergoing cardiac surgery. From these specimens we isolated a high proliferating plastic adherent cell population that, by FACS analysis, expressed mesenchymal markers (CD105, CD44, CD73, CD13 ) and was negative for hematopoietic markers (CD45, CD34) and HLA-DR. Further, in appropriate differentiating media, these cells exhibited osteogenic and adipogenic differentiation as cultures were positive for Oil Red O and Von Kossa staining used to mark intracellular lipid droplets and calcium salts deposits, respectively. Quantitative Real Time (qRT) -PCR analysis revealed that cells were negative for the early cardiac markers Nkx2.5 and Tbx5 and for the adult cardiac markers α-Myosin Heavy Chain and Myosin Light Chain-2a. Interestingly, in standard culture conditions, cells were positive for the early cardiac marker GATA4; in contrast, BM-MSC expressed GATA4 only after dexamethasone treatment. Additionally, when injected into the zebrafish blastula (about 100 –200 cells, n=70), C-MSC specifically homed in the cardiac region, as found at 24 –28 hpf (hours post fertilization). In contrast, transplanted BM-MSCs, were found not only in proximity of the heart, but throughout several mesodermal derivatives of the embryo (n=25). Conclusions: The adult human heart contains C-MSCs that can be easily expanded in vitro and may represent a useful population for autologous cell therapy of some cardiac diseases.