Genetical modification of cardiac Sca-1+ stem cells towards prolonged survival and cardiac differentiation

• Applicant: Privatdozent Dr. Marc-Michael Zaruba
• Subject Area: Cardiology, Angiology
• Term: from 2007 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 56972403

Although the adult mammalian myocardium exhibits some ability to undergo regenerative growth, the decrease in the number of cardiomyocytes (CMs) during cardiovascular disease indicates that the intrinsic renewal rate is insufficient to restore pathophysiologic CM loss. In this regard, it has recently been shown that a population of Sca-1+ stem cells isolated from the adult heart can migrate to the infarct border zone. After homing, approximately 5% of the Sca-1+ cells have at least two fates: some cells fuse to infarct borderzone CMs, while others undergo de novo cardiomyogenic differentiation. The potential regenerative capacity of Sca-1+ derived cardiomyocytes will depend upon their ability to reconstitute significant portions of lost myocardial mass, as well as on their ability to form a functional syncytium. In this application Sca-1+ stem cell transplantation will be combined with several validated cardioproliferative (cyclinD2) and/or cardioprotective (bcl-2) genetic pathways in an effort to increase the number of Sca-1+ derived cardiomyocytes. Additional experiments will monitor intracellular calcium transients in order to determine the degree to which Sca-1+ stem cell-derived cardiomyocytes are able to participate in a functional syncytium with the surviving myocardium.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Loren J. Field