A chemical approach to myocardial protection and regeneration

Abstract

The possibility of generating induced pluripotent stem cells from mouse embryonic fibroblasts and human adult fibroblasts has introduced new perspectives for possible therapeutic strategies to repair damaged hearts. However, obtaining large numbers of adult stem cells is still an ongoing challenge, and the safety of genetic reprogramming with lenti-or retro-viruses has several drawbacks not easy to be addressed. Furthermore, the majority of adult stem cell-based clinical trials for heart regeneration have had generally poor and controversial results. Nonetheless, it is now clear that the injected cells activate the growth and differentiation of progenitor cells that are already present in the heart. This is achieved by the release of signalling factors and/or exosomes carrying them. Along this line, chemistry may play a major role in developing new strategies for activating resident stem cells to regenerate the heart. In particular, this review focuses on small molecule approaches for cell reprogramming, cell differentiation, and activation of cell protection.

Cell-Based Therapies for Cardiac Regeneration: A Comprehensive Review of Past and Ongoing Strategies

“…Several different cell sources have been employed, ranging from bone marrow stem cells to resident cardiac stem cells [ 11 , 12 ]. More recently, direct cardiac reprogramming strategies have been proposed to generate cardiomyocytes starting from terminally committed cells (i.e., dermal fibroblasts), in order to overcome the technical limitations associated with stem cells [ 13 , 14 , 15 ]. Moreover, a direct reprogramming approach could be potentially directly applied in vivo on the scar tissue, reverting the cardiac myofibroblasts into cardiomyocytes and restoring the cardiac functionality [ 16 ].…”