Nine years after the existence of resident Cardiac Stem Cells was first demonstrated, and despite the fact that we
are right now evaluating the preliminary and promising results of the first phase I clinical trials, our understanding of the
mechanisms responsible for cardiac regeneration is still partial and the ability to take advantage of it for therapeutic
purposes can be considered still rudimentary. However, the worldwide urgency of developing new regenerative
therapeutic strategies to reverse the progression of advanced heart failure is funneling a multidisciplinary effort
aimed at better comprehending the biological pathways governing cardiac regeneration.
Therefore, in this paper we are critically reviewing the novel scientific evidences regarding: the multiplicity of
stem cell populations hosted in the heart; the mechanisms regulating the cardiac embryonic development, such as
the epithelial to mesenchymal transition, that may play a part in pathology too; the instructive micro-environmental
factors acting within the Cardiac Stem Cell niche and the information gained from clinical trials. Hopefully the
consideration of all these aspects will yield potential new targets and more effective strategies for cardiovascular
regenerative therapies.
