Hope for Regeneration Through Progenitor Cells

Photo: Mouse heart cells

GFP-iPS cell-derived CPCs (green) injected into
the heart of a living mouse (red), integrate into
functional cardiac muscle tissue. Cell nuclei
are blue; © Fraunhofer IGB

Cardiomyocytes, which are the heart muscle cells responsible for the contraction of the heart, are not able to regenerate after a heart attack. The massive loss of cells and tissue, and the highly restricted regeneration capacity of the adult heart, lead to an impaired blood supply throughout the body that drastically affects a patient’s quality of life. To restore the heart’s function after a major heart attack, clinicians require functionally mature cardiomyocytes that perform like the native cells in the adult heart to replace the cells that were killed.

The production of such functional cardiomyocytes from well-defined cardiovascular progenitor cells (CPCs) is the focus of the research team led by Professor Katja Schenke-Layland from the Fraunhofer IGB in Stuttgart and her colleagues, Doctor Ali Nsair of the University of California Los Angeles (UCLA) and Professor Robb MacLellan of the University of Washington in Seattle, who have now succeeded in identifying such cells in a mouse model.

There has been a significant amount of research effort towards discovering a path for the clinical application of these cells in patients. The reason for the lack of success is that the markers that help to identify CPCs, such as Islet1 or Nkx2.5, are located in the nucleus of the cells. The use of these cell markers modifies the cells rendering them therapeutically unusable, making the identification of safe cell-surface markers essential.

On this task, the research team of Schenke-Layland, MacLellan and Nsair focused their research. With success: They were able to identify two markers, the receptors Flt1 (VEGFR1) and Flt4 (VEGFR3), on the surface of CPCs with which these cells can be clearly identified while fully preserving their biological function. This discovery allows scientists to isolate clinically relevant cardiovascular progenitor cells that can be functionally matured.

The result of the group provides the first opportunity to generate functioning heart muscle cells, which integrate into the heart muscle. "We are currently focusing on research with human iPS cells. If we can show that cardiovascular progenitor cells can be derived from human iPS cells that have the ability to mature into functional heart muscle, we will have discovered a truly therapeudic solution for heart attack patients", Layland hopes.

MEDICA.de; Source: Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB