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ePaper created 2013-09-24, 11:56:35 | version 1.25.20
66 MEDICINE DEVELOPING BIOLOGICALLY INSPIRED CAR- DIOVASCULAR REGENERATIVE TECHNOLOGIES Prof. Dr. rer. nat. Katja Schenke-Layland, Shannon Lee Layland B.A. Despite significant advances in cardiology and cardiac surgery, cardiovascular disease remains one of the leading causes of the death in the world. In Europe alone, an estimated 10 mil- lion people are affected each year. The most common cause of heart failure is either acute or chronic damage to the heart. The human heart possesses very little regenerative capacity. After a cardiac event, the loss of heart function cannot be naturally recovered, which permanently and drastically impairs the quality of life of patients. Therefore, restoration of normal heart function after the heart has been damaged is a driving goal for a variety of researchers worldwide. Deriving cardiomyocytes from cardiovascular progenitor cells Cardiomyocytes as well as endothelial and smooth muscle cells evolve during the embryonic development of humans and other mammals from what are defined as cardiovascular progenitor cells (CPCs). CPCs have been of great interest in the field of biomedical research, but to date, have not been translated to clinical settings. CPCs can be identified using cell markers. Typical CPC markers, such as Nkx2.5, are located within cells. The use of such internal cell markers damages cells, leaving them therapeutically unusable. The lack of a cell marker that does not damage CPCs, such as a cell surface marker, has hindered the use of these potent cells in the clinic. Therefore, the search for CPC surface markers is of great re- search interest. Surface markers for identifying cardiovascular progenitor cells Together with our partners, Professor Ali Nsair of the Univer- sity of California Los Angeles (UCLA) and Professor W. Robb MacLellan of the University of Washington in Seattle, we are now able to identify surface markers for living and functional CPCs in the mouse that allow for their isolation and expansion [1]. Through gene expression analysis, the team identified the combination of receptors Flt1 (VEGFR1) and Flt4 (VEGFR3) as suitable surface markers for CPCs. Producing cardiovascular progenitor cells from induced- pluripotent stem cells In further studies, we were able to produce the first Flt1-/ Flt4-positive CPCs from clinically relevant, induced-pluripotent stem cells (iPSCs), which could develop into endothelial cells, smooth muscle cells and functional, beating cardiomyocytes. We used the iPSC method for which the Japanese scientist Shinya Yamanaka was awarded the 2012 Nobel Prize for Med- icine. He published, just 6 years ago, that only four proteins are responsible for the pluripotency of mouse embryonic stem cells [2]. He brought the four genes into differentiated – ma- ture and specialized – body cells, which then programmed the adult cells back to an embryonic state. From these cells, which he called iPSCs, specialized cells, such as liver and nerve cells or cardiomyocytes can be developed. 1