Adult Cardiac Stem Cell Aging: A Reversible Stochastic Phenomenon?

Figure 2

c-Kit^pos CSCs are multipotent in vitro and in vivo. (a) Undifferentiated c-kit^pos (green) CSC-derived cardiospheres express multipotent stemness markers (c-kit, Oct-4, Sox-2, Klf-4, and Nanog) and Wnt3a (red). Bar = 50 μm. (b) CSC-derived contracting CMs in vitro express contractile proteins (actinin, cTnI, MHC, and cardiac actin) with coexpression of cardiac transcription factor (Gata-4). The CSC-derived CMs exhibit well-defined sarcomeric structures (z lines and dots) as well as gap junction formation (Cnx-43) between cells. DAPI stain nuclei are in blue. Bar = 20 μm. (c) Light microscopy image of freshly isolated adult cardiomyocytes from a dissociated rat heart 28 days after myocardial infarction (MI) and CSC GFP injection (MI + CSC GFP) shows a CSC-derived GFP-positive cardiomyocyte. (d) Confocal microscopy images show host-derived preexisting GFP^neg cardiomyocytes as compared to CSC-derived GFP^pos cardiomyocytes isolated from MI + CSC GFP rat hearts at 28 days after MI. Note that GFP^pos cardiomyocytes are of smaller size and mononucleated when compared to surviving binucleated GFP^neg cardiomyocytes of the host. (e) Representative confocal images show at high magnification a CSC-derived newly formed GFP^pos cardiomyocyte in the infarct border zone 28 days after MI treated with CSC GFP. Figure 2 is reproduced from Carla Vicinanza et al., (under the Creative Commons Attribution License/public domain) [55].