Cardiac stem cells: A new potential tool for cardiac repair?

Abstract

Background: The current therapy for myocardial infarction (MI) is not adequate enough, since mortality after MI remains very high. Cardac repair by injection of stem cells is a promising therapy. Previously, several clinical studies using bone marrow stem cells were undertaken to explore the possibilities of stem cell therapy. Meanwhile, more evidence emerges that cardiac stem cells (CSCs) are present in the adult human heart. These CSCs are claimed to be actual stem cells residing in the heart and not just bone marrow stem cells mobilized to the heart. Therefore, CSCs are probably better suited for cardiac repair, since they are most likely already "pre-programmed" to become cardiomyocytes. Aim. To support this hypothesis, the aim of our study was to isolate human CSCs and compare them phenotypically and functionally with human mesenchymal stem cells (MSCs). Design and methods. For the isolation of CSCs the two main methods described by Messina et al. and by Anversa et al. were followed. Messina et al. defines CSCs as cardiosphere derived cells (CDCs), which can be obtained by culturing phasebright cells that appear after two weeks in a culture of cardiac explants. On the contrary, Anversa et al. consider c-kit+ cells isolated from cell outgrowth from a cardiac explant as CSCs. Upon isolation, CDCs, c-kit+ cells and MSCs appeared to be morphologically very similar in culture. Therefore, different panels of antibodies were used to phenotypically characterize these three cell types. Results. CDCs, c-kit+ cells and MSCs were found to be positive for CD13, CD29, CD44, CD55, CD90, CD49c, CD73, CD105 but negative for CD34, CD45 and CD133. The main difference between cells isolated from heart tissue and MSCs was that only MSCs stained positive for CD140b. For the functional analysis, cells were subjected to a stem cell differentiation assay. While MSCs could easily differentiate to adipocytes, osteocytes, and chondrocytes, CDSs could not. In addition, the possibility of differentiation into cardiomyocytes was examined. Therefore, cells of all three populations were cultured in differentiation medium containing 2% FCS and 5-aza, DMSO or TGF-b respectively. To investigate differentiation, cells were harvested and analyzed for expression of cardiomyocyte specific genes by RT-PCR. Preliminary results from these monocultures indicated that cells isolated from heart tissue had more potential to differentiate into cardiomyocytes than MSCs, because the former cell populations expressed cardiac troponin T and b-actinin in these conditions while the MSCs did not. Conclusions. These results indeed suggest that there is a phenotypical and functional difference between CSCs and MSCs, but further investigations have to be performed to show that these CSCs are able to differentiate into cardiomyocytes in vitro and in vivo.