Role of reactive oxygen species in the regenerative capacity of c-kit+ cardiac precursor cells
- Owing in large part to the low regenerative capacity of the heart, cardiac disease remains the leading cause of death in the developed world. Compelling evidence now suggests the presence of small populations of stem cells residing in the postnatal and, to a lesser extent, in the adult myocardium. These cardiac progenitors have been isolated based on specific marker expression including c-kit, a receptor tyrosine kinase.
- Our research corroborates existing evidence regarding the stemness of c-kit and demonstrates that c-kit identifies a progenitor population in the postnatal heart that can be differentiated in vitro into all three lineages that specify the heart. Research also suggests that redox mechanisms play critical roles within stem cell niches, making these mechanisms important targets in cardiac cell-based therapy since they mediate signaling pathways necessary for successful engraftments.Â
- We believe that maintaining a low reactive oxygen species (ROS) state in transplanted stem cells and protecting them from excessive ROS may enhance their regenerative potential.Â Therefore, understanding the sources of ROS and their function in cardiac progenitor cells, along with developing antioxidant therapies, may be critical for successful cell-based therapy.
- In order to determine the redox genes important to c-kit cell function, we have utilized RT2Profiler PCR Arrays to investigate the mRNA expression levels of 84 genes involved in mouse oxidative stress and antioxidant defense systems. These data reveal a highly unique redox profile in c-kit+ progenitors and may provide genetic targets for improving cell survival, proliferation and/or differentiation following cardiac damage.