Inject Me Once and Inject Me Twice. Then Inject Me Once Again.

Although nature may be subtle, our interventional approaches to enhancing myocardial regeneration can be anything but. We genetically re-engineer cells to enhance their potential, reprogram cells from one type to another, apply patches of cells like plaster on a wall, or inject unfathomable numbers of cells hopeful that a small fraction cling to the heart and to life long enough to make a difference. All such interventions intend to prolong and improve on the relatively modest gains in myocardial structure and function repeatedly observed with adoptive cell transfer therapy using various experimental models, cell types, and delivery routes. Clearly, the weight of the evidence supports the assertion that cell therapy can confer beneficial effects, but consensus opinion is that the degree of improvement generally falls markedly short of what is needed for full restoration of hemodynamic performance and that we need to do better. And in this next installment of approaches to tweak the Natural Order of things, Tokita et al lend a hand by offering Nature the opportunity to repeat herself.