In vitro transdifferentiation of human endothelial progenitor cells into cardiac myocytes: determination of the underlying mechanisms

• Applicant: Professorin Dr. Stefanie Dimmeler
• Subject Area: Pediatric and Adolescent Medicine
• Term: from 2002 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5377827

Cell therapy for the treatment of cardiovascular disease is a promising option to replace cardiomyocytes. Recent studies provide evidence that differentiated cells can transdifferentiate into other lineages. We demonstrated that human endothelial progenitor cells (EPCs), isolated from the peripheral blood of adult volunteers, are capable of trans-differentiating into cardiac myocytes (CM) in vitro when co-cultivated with rat neonatal CM. Further studies now shall elucidate the underlying mechanisms for transdifferentiation of EPCs to CM with emphasis on intercellular communication via Gap-junctions and cadherins. Adjacent cells are connected by Gap junctions. Therefore, the present study will assess 1) whether Gap junctions are required for the cell-to-cell communication and transdifferentiation of EPCs, and 2) which connexins are involved in this process. Cadherins are transmembrane glycoproteins mediating cell-cell adhesion, which can participate in signaling events leading to differentiation. Therefore, we plan to investigate the involvement of cadherins for the transdifferentiation of EPCs. Finally, the reprogramming of EPCs should be time-dependently determined by gene expression arrays to get insights into the sequential activation of genes essential for EPC transdifferentiation into cardiomyocytes.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1109: Embryonal and Tissue-Specific Stem Cells - Regenerative Systems for Cell and Tissue Repair
• Participating Person: Dr. Cornel Badorff