Adipose derived stromal cells in cardiovascular regenerative medicine

Cardiovascular diseases are the leading cause of death globally. Myocardial Infarction occurs due to the occlusion of one of the branches of the coronary artery system. Once the coronary artery occludes, the downstream myocardium is deprived of oxygen and nutrition, which lead to myocardial ischemia. Prolonged ischemia results in the death of cardiomyocytes and surrounding vasculature. Subsequently, the death signals from apoptotic and necrotic cells activate rapid inflammatory reaction, which dominates the early post-MI microenvironment. A promising approach for induction of cardiac repair is cell-based therapy. Recent clinical trials with intramyocardial injection of freshly isolated ADSC demonstrated improvement of cardiac parameters, increased revascularization and finally the quality of life. In this thesis we acquired better understanding of use of Adipose-tissue Derived Stem/Stromal Cells in post-myocardial infarction therapy. We have shown that in contrast to the previous paradigm, therapeutic cells of mesenchymal origin such as ADSC gain higher regenerative potential under hypoxic and pro-inflammatory conditions, which render them the most promising cells for cardiac therapy. We have identified that not only ADSC but their secreted factors in the conditioned medium or deposited extracellular matrix enhance cardiomyocyte proliferation, organization and maturation as well as lead to increased vascular network formation. The use of ADSC or ADSC-secretors could help to overcome the limitation of cardiac cell therapy as well as offer of-the-shelf product for immediate application. We propose that use of ADSC or ADSC-derived conditioned medium or extracellular matrix components based therapy is feasible and clinically relevant option for treatment of post-MI complications