Abstract
Stem cell and regenerative approaches that might rejuvenate the heart have immense intuitive appeal for the public and scientific communities. Hopes were fueled by initial findings from preclinical models that suggested that easily obtained bone marrow cells might have significant reparative capabilities; however, after initial encouraging pre-clinical and early clinical findings, the realities of clinical development have placed a damper on the field. Clinical trials were often designed to detect exceptionally large treatment effects with modest patient numbers with subsequent disappointing results. First generation approaches were likely overly simplistic and relied on a relatively primitive understanding of regenerative mechanisms and capabilities. Nonetheless, the field continues to move forward and novel cell derivatives, platforms, and cell/device combinations, coupled with a better understanding of the mechanisms that lead to regenerative capabilities in more primitive models and modifications in clinical trial design suggest a brighter future.
Highlights
The heart is traditionally considered a post-mitotic organ with limited, if any, reparative capacity
This led directly to the study of the use of readily available stem cell sources to enact cardiac repair with some dramatic and perhaps surprising reports of improvements in left ventricular function [7]. These experiments, which in some cases appeared inconsistent with clinical experience, raised several questions including the question of why bone marrow cells, which circulate through end-organs naturally at many times the doses administered in these studies, would affect such effective regenerative improvements
Even amongst patients who present with shock and survive to a time point at which stem cells are conventionally administered, the risk of myocardial infarction, cardiac death, or re-admission for heart failure is relatively low [40]; it no longer appears that acute myocardial infarction is an attractive target for regenerative approaches
Summary
The heart is traditionally considered a post-mitotic organ with limited, if any, reparative capacity. While considerable effort is being expended to better understand the mechanism(s) whereby organisms such as zebrafish effect cardiac regeneration, initial clinical development was driven by the rather surprising discovery that many adult tissues, including the post-mitotic organs like the heart, house resident stem cells that could transdifferentiate into mature cells [4,5,6]. This led directly to the study of the use of readily available stem cell sources to enact cardiac repair with some dramatic and perhaps surprising reports of improvements in left ventricular function [7]. 30,000-foot (and perhaps mistakes) made to date, and to discuss paths forward and promising technologies that that may may yet fulfill the promise of regenerative approaches to treatment of technologies heart disease
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