Cardiac Cell Replacement Therapy

Cardiovascular diseases in general and ischaemic heart disease (IHD) in particular are the most frequent cause of death worldwide. Cardiac infarction can be a consequence of IHD and is caused by complete occlusion of a coronary vessel resulting in the loss of large numbers of cardiac myocytes, the formation of a non-contractile scar tissue. The loss of cardiac function can progressively develop into heart failure.

Cardiac cell replacement therapy aims at partially (or even fully) restoring the pumping function of the diseased organ. We have focussed on the use of cardiomyocytes derived from induced pluripotent stem cells (iPS-CMs) to engineer heart tissue in vitro and in vivo.

In earlier studies we have explored the integration of CMs into artificial (collagen-based) and native cardiac matrix and were able to identify low adhesion to these matrices as a potential cause for the low engraftment rate of iPS-CMs. Matrix producing cells such as embryonic fibroblasts or adult bone marrow-derived mesenchymal stem cells (bMSCs) could overcome this hurdle and facilitate the cell engraftment. Together with our partners these findings could be confirmed in vivo showing that micro-tissues engineered from iPS-CMs and bMSCs show increased engraftment of iPS-CMs. Our interest is to develop the method further in a large animal model of cardiac infarction to test it´s relevance for future clinical application. In parallel we explore new strategies to engineer cardiac tissue in vitro that is suitable to be applied as a patch in vivo.