Since the first clinical trial conducted by Menasché and colleagues in 2008 (Circulation. 2008), more than 100 trials involving stem cell therapy for the treatment of myocardial infarction have been reported. Different adult stem and progenitor cells including mononuclear cells, endothelial progenitor cells, and mesenchymal stem cells have shown to be safe in humans; yet, their clinical potential remains inconclusive. The enthusiasm surrounding regenerative medicine in the heart has been dampened by the reports of poor survival, proliferation, engraftment, and differentiation of the transplanted cell. In fact, it has become increasingly accepted that stem cells exert beneficial effects (cell survival, angiogenesis, cardiac remodeling) mainly through the release of biologically active molecules acting in a paracrine fashion on cardiac resident cells. On the other hand, recent investigations have demonstrated that stem cell potential is found to be reduced in the presence of cardiovascular risk factors partly explaining the relatively low effectiveness of autologous-based stem cell therapies.
Based on current achievements it is evident that cell-based therapies still require significant progress before they can be incorporated into daily clinical practice to fight against ischemic heart disease. Many problems need to be resolved including the identification of the best cell source, the optimal delivery strategy, the timing and dosages. Additionally, progenitor/stem cells still need to be fully characterized. In this regard, recent advances in stem cell biology and in transcription factor-based reprogramming strategies may provide exciting solutions to overcome many of the challenges and limitations that currently hamper cell-based therapies.
At present, different strategies aimed to enhance stem cell potential and survival such as stem cell pre-conditioning, genetic modifications, and microenvironment modulation are a matter of intense research. Moreover, combination of stem cell therapy and bioengineering techniques hold great potential to improve stem cell transplantation.
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