Figure 1. Conceptual paradigm of repeated cell therapy.

A. Following cell administration, the number of transplanted cells in the myocardium falls rapidly⁸ but a small number persist for many weeks (at least 1 year).⁷ Repeated cell doses produce a cumulative increase in the number of transplanted cells that persist long-term in the myocardium (red area).^11,12 Each cell dose produces a burst of EV release (B), which is responsible for the cumulative therapeutic effects (C). The cumulative increase in long-lasting exogenous cells (red area) may be associated with a cumulative increase in sustained EV release by these cells (blue area). Panels A and C are based on experimental data^11,12; panel B is speculative.