Present data indicate that intracoronary injection of enriched BMSC is associated with greater in-stent proliferation and larger luminal loss in non-stented IRA segments that result in a significant decrease in pressure-derived FFR. These changes are consistent with decreased epicardial conductance of the IRA, owing to diffuse luminal loss and increased plaque burden. Our study suggests several mechanisms for the “Janus-like” effect. First, the total number of CD34+ or CD133+ cells in the cell suspension was higher than in previous studies (5- 11), and patients with a higher number of injected CD133+ cells showed a larger luminal loss of distal non-stented segments. Hence, dose-dependent increase in local concentrations of pro-angiogenic molecules might have exacerbated pro-atherogenic effects. Second, cell-treated patients with in-stent restenosis or a de novo stenosis showed lower levels of interleukin-10 and higher levels of serum VEGF-A, suggesting disequilibrium between pro-atherogenic and anti-atherogenic factors as a predisposing factor. Nevertheless, local concentration of inflammatory cytokines or biological activity of CD133+ could provide further insights into these hypotheses. As an alternative mechanism, in-stent proliferation might be related to repetitive balloon occlusion at the time of the cell injection, albeit at low inflation pressure, by impairing ongoing re-endothelialization. Note that earlier studies (6,14) demonstrated immunological safety of immunomagnetic isolation with absence of human anti-mouse antibodies after stem cell enrichment in bone marrow transplant patients, which argues against immunological response as the underlying mechanism.