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ABSTRACT
Introduction: The characterization of multipotent endogenous cardiac stem cells (eCSCs) and the breakthroughs of somatic cell reprogramming to boost cardiomyocyte replacement have fostered the prospect of achieving functional heart repair/regeneration.
Areas covered: Allogeneic CSC therapy through its paracrine stimulation of the endogenous resident reparative/regenerative process produces functional meaningful myocardial regeneration in pre-clinical porcine myocardial infarction models and is currently tested in the first-in-man human trial. The in vivo test of somatic reprogramming and cardioregenerative non-coding RNAs revived the interest in gene therapy for myocardial regeneration. The latter, together with the advent of genome editing, has prompted most recent efforts to produce genetically-modified allogeneic CSCs that secrete cardioregenerative factors to optimize effective myocardial repair.
Expert opinion: The current war against heart failure epidemics in western countries seeks to find effective treatments to set back the failing hearts prolonging human lifespan. Off-the-shelf allogeneic-genetically-modified CSCs producing regenerative agents are a novel and evolving therapy set to be affordable, safe, effective and available at all times for myocardial regeneration to either prevent or treat heart failure.
Article highlights
Cardiovascular disease (CVD) represents the main cause of mortality in the western world;
There is no currently available therapy to regenerate the loss of cardiomyocytes occurring after an acute myocardial infarction.
Cardiac stem cells (CSCs) are able to regenerate functional myocardial tissue when exogenously administered or through their in situ activation.
The direct fibroblast reprogramming allows the conversion of non-cardiac somatic cells into cardiomyocytes.
Genome editing can be employed to specifically on-site modify regenerative products/agents.
Non-coding RNAs can target endogenous cardiac regeneration as well as somatic cardiac cell myogenic reprogramming.
Cell and Gene therapy approaches can be combined to optimize the transient engraftment, survival and paracrine effects of donor allogeneic CSCs, enhancing their ability to foster the endogenous regenerative potential for the injured heart.
This box summarizes key points contained in the article.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose