14:00-14:45

Smart Microtissues for Cardiac Repair

Myocardial infarction (MI) causes massive loss of cardiomyocytes, leads to formation of fibrotic tissue and induces a hypertrophic response in the survivin myocytes, resulting in impaired cardiac function. Current therapy consists of restoration of perfusion and pharmacological treatment to improve the function of the remaining viable cells and to prevent the development of heart failure. Cell transplantation therapy has been put forward in recent years as an alternative approach to reduce cell damage and improve tissue perfusion by generating new vessels. Currently, many cell transplantation protocols are being executed, but most protocols have no or a modest beneficial temporary effect. The explanation for these disappointing results is: inappropriate cell type, high level of cell death and poor engraftment following injection, insufficient vasculogenesis and inadequate cell delivery routes. After a medium-size left ventricular infarct, an average of 2x10⁹ myocytes is lost. Cell replacement strategy should therefore deliver 10⁸-10⁹ cells. In order to avoid immunogenicity, the cell type should preferentially be autologous, with a certain degree of plasticity, enabeling generation of new myocytes and new vessels. Cell delivery via intramyocardial injection or via the coronary circulation is inefficient and causes > 90% cell loss at the moment of injection, with little differences between intramyocardial, intracoronary or retrograde venous delivery. Furthermore only a small fraction of the cells delivered survives and contributes to some therapeutic effect. So not only an optimal cell source should be identified, but also new strategies to deliver and increase homing and survival of the injected cells should be developed. Therefore, we aim to improve cardiac function in patients suffering from heart failure, by autologous cell based microtissue delivery. We are exploring the growth, cardiomyogenic and vasculogenic potential of cardiomyocyte progenitor cells and mesenchymal stem cells. Furthermore, we are developing bioactive microtissues, that should enforce homing, survival and function of cardiomyocytes and angiogenic cells. Finally, to determine the optimal application route of autologous microtissues we analyze graft cell survival and improvement of cardiac function in the pig model for myocardial infarction.

Speaker

Prof. Marie-Josè Goumans, Department of Molecular Cell Biology, Leiden University Medical Center, Netherlands

Chair

Dr. Giancarlo Forte, MANA Scientist, NIMS