This study shows that local preirradiation of infarcted myocardium markedly improves donor cell engraftment after myocardial infarction. Using a rat model of permanent coronary artery ligation, the authors applied catheter-based high-dose-rate brachytherapy to a delimited region of the infarct one day before intramyocardial transplantation of ZsGreen-labeled induced pluripotent stem cells (iPSCs). Quantitative histological analysis demonstrated a dramatic increase in engrafted cells in irradiated hearts compared with non-irradiated controls (median ZsGreen⁺ area ≈315,000 vs. 12,000 µm²; p < 0.0001), corresponding to an ~26-fold enhancement of engraftment, without detectable microstructural cardiac damage or major adverse events. Mechanistically, the authors propose that irradiation reduces the activity and competitiveness of endogenous proliferating cells within the infarct niche, thereby facilitating donor cell retention and survival, an effect previously described in other tissues but not in the heart. The study concludes that local cardiac tissue preconditioning by irradiation is a feasible strategy to substantially improve cell engraftment and may enhance the effectiveness of future cardiac cell-therapy approaches, although functional recovery was not directly assessed in this proof-of-concept work.
Abizanda et al. (Sun,) studied this question.