Abstract
Although somatic stem cells have been reported to exist in various adult organs, there have been few reports concerning stem cells in the heart. We here demonstrate that Sca-1-positive (Sca-1+) cells in adult hearts have some of the features of stem cells. Sca-1+ cells were isolated from adult murine hearts by a magnetic cell sorting system and cultured on gelatin-coated dishes. A fraction of Sca-1+ cells stuck to the culture dish and proliferated slowly. When treated with oxytocin, Sca-1+ cells expressed genes of cardiac transcription factors and contractile proteins and showed sarcomeric structure and spontaneous beating. Isoproterenol treatment increased the beating rate, which was accompanied by the intracellular Ca(2+) transients. The cardiac Sca-1+ cells expressed oxytocin receptor mRNA, and the expression was up-regulated after oxytocin treatment. Some of the Sca-1+ cells expressed alkaline phosphatase after osteogenic induction and were stained with Oil-Red O after adipogenic induction. These results suggest that Sca-1+ cells in the adult murine heart have potential as stem cells and may contribute to the regeneration of injured hearts.
Highlights
The heart has long been thought to adapt to increased work and loss of cardiomyocytes by the cellular hypertrophy of residual cardiomyocytes, but not by the proliferation of mature cardiomyocytes or the differentiation of undifferentiated cells
Cell Surface Antigens of Sca-1ϩ Cells Derived from the Adult Murine Heart—Flow cytometric analysis revealed that Sca-1ϩ cells were enriched to over 90% when adult murine cardiac cells were sorted twice with the Magnetic Cell Sorting (MACS) system using PE-conjugated anti-Sca-1 antibody and anti-PE micro beads (Fig. 1A)
Transient treatment with 5Ј-azacytizine induced expression of cardiac genes in Sca-1ϩ cells, it did not induce expression of cardiac troponin T, assembly of sarcomere or spontaneous beating. These results suggest that treatment with 5Ј-azacytizine induces differentiation of Sca-1ϩ cells into cardiomyocytes incompletely and that oxytocin is a more potent inducer of cardiac differentiation than 5Ј-azacytizine
Summary
We first report that a novel population from Sca-1ϩ cells derived from the adult murine heart proliferates and differentiates into beating cardiomyocytes with oxytocin treatment
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