Therapy after Myocardial Infarction: repair by stem and progenitor cell mobilization and transfer
Supported through the ECīs 7th Framework Program through Grant Agreement No: HEALTH-F2-2009-222995
A key problem in repair and functional regeneration following myocardial infarction is the inability of heart muscle tissue to regenerate itself and appropriate vascularization under conditions of increased strain caused by the reduced contractibility of the damaged heart. This frequently leads to continuous loss of functional cells, further increase of the infarct area and finally complete loss of heart function.
We propose in this project to explore possibilities for cell therapy using different procedures and sources of stem and progenitor cells. First, we will investigate factors stimulatory for stem/progenitor cells from different sources, their recruitment to the heart and the activation of resident heart stem cells. Second, we will evaluate adoptive transfer of stem/progenitor cells, from bone marrow, adult and cord blood, adipose tissue and heart tissue itself. The use of ex vivo cultured and differentiated cells including embryonic stem cells will be tested. Third, we will test genetic modification of these cells for improved differentiation, homing and tissue repair. Fourth, we will use a unique artificial scaffold material as a slow release device for factors and as a structural support material for providing the different cell preparations to the damaged areas. This scaffold will also be used for tissue engineering in vitro followed by insertion of artificial tissue onto the infarct area.
Fig.1 : Overview of principle potential mechanisms of heart tissue repair. Important mechanisms and cell sources for revascularization and regeneration of myocardium that could be activated and/or used for cell therapy are depicted. (MAPC: multipotent adult progenitor cell; MSC: mesenchymal stromal cell; CEP: ciculating endothelial precursor)
This project is on the one hand of high clinical importance, on the other hand is designed to support the research and development needs of two SMEs, one of which is determined to become a supplier of growth factor cocktails for clinical stem cell culture, a second is based on the generation and supply of stem cells for clinical use.
In summary, the project will evaluate whether induction of repair by factors, adoptive transfer of stem/progenitor cells or engineered tissue has a benefit for heart regeneration, and has the potential to become a future clinical standard therapy.