Stem cell maintenance and homeostasis in the ageing heart

The objectives of this study are to investigate the role of SPARC and desmin in the maintenance of self-renewal and differentiation of cardiac stem cells in the ageing heart. Cardiac stem cells are found at various places in all cardiac tissues and seem to contribute to homeostasis throughout life. Expression of desmin in these cells causes not only upregulation of myocardial transcription factors such as Nkx2.5 but also of the matricellular protein SPARC. SPARC is a secreted protein modulating the extracellular matrix during ageing but also fulfilling a barely described cell-autonomous and nuclear function which is the main subject of this study. Preliminary results suggest a positive feedback loop between desmin and SPARC, which may contribute to the continuous expression and secretion of SPARC. Thus SPARC may influence the stem cell niche and significantly contribute to fibrosis and remodelling during ageing and cardiac diseases. Understanding these processes very likely will contribute to new cardiac therapies.

The extracellular matrix and cytoskeleton of cardiac stem cells contribute significantly to maintaining cardiac function in old age.