Cell or Cell Products, which Would Rescue Cardiovas-cular Regenerative Medicine?

Ischemic heart conditions are one of the top categories in the world health complications accounting for high mortality rates which estimated to be about ۳۰% worldwide. Common thera-peutic approaches including medications or device therapy have been widely used and been the option of choice for cardi-ologists resulting in fairly good outcomes. However, these ap-proaches could not induce mascularization in the ischemic heart region and inhibition of progression into heart failure, possibly to its end stage which necessitates heart transplantation as the only remaining option. While heart transplantation is continued to be very challenging due to the shortage of organ donor. The ۲۱st century has been beginning of a very promising era in the field of medicine as novel therapeutic approaches have been introduced, researched and found its way to the clinics particu-larly for diseases with no effective treatment. Cell therapy is one of these novel therapeutic approaches that attracted high attention and has been widely experimented for diseases with no efficient cure including ischemic heart conditions. Differ-ent modalities of cell therapy have been employed for ischemic heart diseases including multiple cell types, various dosing and delivery means. Although promising, the results of clinical trials seems to be confounded by inter-trial and inter-patient variabil-ity making an accurate conclusion challenging. And exactly for this reason, the recommendation of any cell type or dosing has been missing so far. Furthermore, although the results of mes-enchymal stem cell therapy were promising for ischemic heart conditions, but still not relevant enough to be translated and be routinely used in clinics. In parallel to investigate cell therapy, interest in cell products’ therapy of myocardial infarction (MI) has followed due to the potential of such modalities for clini-cal translation, high replicability and off-the-shelf accessibility. One of these promising approaches is transplantation of extra-cellular vesicles (EVs) to infarcted heart tissues. EVs include microvesicles (MVs), apoptotic bodies and exosomes. It has been shown that therapeutic efficacy of cardiac cell therapy was to a great extent due to EVs. EVs carry functional proteins and various types of RNA that can inhibit remodeling in the infarcted myocardium. In general, the insufficient efficacy of cell or cell products therapy so far has been mainly ascribed to limited potencies of these novel therapeutic agents, limited re-tention after delivery, and disease heterogeneity. Thus, ongoing efforts are made to achieve to the best setting including best cell source with maximal biotherapeutic potency or best cell source products, standardized dosing, the most feasible and efficient delivery system, and last but not least the appropriate target re-sponsive patient populations.