Myocardial Regeneration for Humans　― Modifying Biology and Manipulating Evolution ―

Abstract

Cardiovascular disease remains the leading cause of death worldwide and developing novel therapies to treat and cure the disease remains a high priority in the healthcare research community. Adult stem cells were successful in entering numerous clinical trials over the past 15 years in attempts to regenerate the heart. First-generation adult stem cell therapies for myocardial regeneration were highly promising in small animal models but realized benefits in humans were far more modest. Consequently, second-generation therapeutic approaches in early implementation phases have focused on enhancing cellular properties with higher survival and regenerative potential. Genetic programming dictates cellular fate, so understanding genetic composition and responses at the gene level to influence the outcome of the cell is essential for successful outcomes in regenerative medicine. Genetic editing is at the forefront of scientific innovation and as basic scientific research continues to expand upon understanding eukaryotic regenerative themes, a clearer vision of the possible future therapeutic approaches can be realized. Ultimately, enhancing biology and manipulating evolutional selection of cellular properties will be critical to achieving clinically relevant and biologically meaningful cardiac regeneration.

Cardiac interstitial tetraploid cells that escape replicative senescence are found in rodents but not large mammals

“…While the ultimate role of polyploidy in the CIC population remains to be determined in future studies, the findings in this report establish the benchmark of distinct DNA content differences between rodent and large mammals. We hypothesize an endogenous response within rodent mammals lacking in larger mammals contributes to the blunting of injury along with enhanced capacity for repair 86 . Future studies regarding fresh isolate human lineage-ckit+ CICs may provide additional insights into differences between endogenous human and rodent samples.…”

How to Stimulate Myocardial Regeneration in Adult Mammalian Heart: Existing Views and New Approaches

“…In order to further improve the myocardial regeneration process, CSC preconditioning with growth factors, hypoxic shock, or proliferation and differentiation stimulants has also been applied. CSC genetic modification, which is used to improve specific features among SCs, represents another attempted advanced therapeutic method [25]. However, despite temporary signs of improvement with regard to cell survival, no significant heart regeneration was observed in any case.…”

Remodeling the Human Adult Stem Cell Niche for Regenerative Medicine Applications

“…Future models may expand into gene therapies: the analysis of mononuclear polyploid cells naturally occurring in regenerative tissues represents a more recent approach [ 96 ].…”