Influence of extracellular matrix components on cardiac progenitor cell-mediated myocardial regeneration

• Applicant: Dr. Mathias Konstandin
• Subject Area: Cardiology, Angiology
• Term: from 2009 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 116388660

Heart failure is the leading cause of mortality in western countries. Discovery of resident multipotent cardiovascular progenitor cells (CPCs) in mammalian adult heart raises hope for autologous cell therapy. Injection of ex vivo expanded CPCs in border zones of myocardial infarcts in rodents improves cardiac function possibly related with formation of de novo cardiac muscle and blood vessels within scar tissue. Further improvement is mediated by over-expression of Pim-1 in adoptively transferred CPCs. The PI3K/Akt/Pim-1 signaling axis is a pivotal protective pathway in many cell systems. In non-cardiac cells integrin-mediated signals from the extracellular matrix (ECM) lead to Akt activation. So far little is known about these signals leading to activation of the Akt/Pim-1 cascade in CPCs. Goal of the proposal is to investigate in detail the crosstalk between ECM and CPCs. It is proposed that a systematic analysis of ECM components on Akt/Pim-1 signaling in CPCs may improve myocardial regeneration through improved cellular survival and commitment to cardiogenic lineages. CPC functions as proliferation, apoptosis, adhesion and transmigration will be determined after ECM treatment in vitro. After optimal ECM manipulations are determined, in vitro findings will be tested in vivo, using a mouse myocardial infarction model. These studies will have potential relevance for future treatment of heart failure through cell-based therapies.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Mark Sussman