No abstract

Bone marrow (BM) cells may interact with coronary endothelium and modulate coronary atherosclerosis. We investigated the time course of coronary luminal loss and changes in conductance after intracoronary injection of enriched hematopoietic BM stem cells in patients with previous myocardial infarction (MI). Among 24 patients with acute MI, 13 were randomized to early (<7 days) and 11 to late (4 months) intracoronary injection of CD133 + cells after the infarction. Segmental quantitative coronary angiography and fractional flow reserve (FFR) measurements of the infarct-related (IR) artery (A) and contralateral artery (control) were performed. In the early group, at 4 months, cumulative luminal loss (LL) of the minimal luminal diameter (MLD) of the IRA distal to the stented segment was −0.39 (−0.51-0.10) mm (p < 0.05 vs. control). There was no further change in LL between 4 and 8 months [−0.09 (−0.26-0.15 INTRODUCTIONinfused early after myocardial infarction, exerted beneficial effects on cardiac recovery in patients with reperfused myocardial infarction, but they appeared to be asCell-induced angiogenesis is mainly mediated by paracrine effects through the release of cytokines, adhesion sociated with higher luminal loss of downstream distal segments at 4 months follow-up. Therefore, we investimolecules, and growth factors. However, similar cytokines and molecules participate in pathogenesis of athgated long-term effects of intracoronary CD133 + -enriched cells on luminal loss of distal nonstented segments of erosclerosis, and striking similarities in the molecular mechanisms underlying both processes are well docuthe infarct-related artery in a separate group of patients with recent myocardial infarction treated with stented mented (6). Furthermore, opposing effects on angiogenesis and atherogenesis were observed in studies using angioplasty randomized to early and late stem cell treatment. cytokines or growth factors involved in both processes (5,8,9,13,17,21). This led to the hypothesis that interre- MATERIALS AND METHODS lated tradeoffs may be inherent to therapies designed toPatients and Study Protocol enhance collateral formation (6). The concept coined as "Janus-like" phenomenon (6) may have important cliniThe study population consisted of 24 patients with acute myocardial infarction (MI) due to occlusion of the cal implications for intracoronary stem cell therapy. In our previous studies (1,14), CD133 angioplasty. All patients underwent cardiac catheterizaCardiac Catheterization tion between 5 and 7 days after the infarction (baseline), LV volumes and ejection fraction were calculated usand at 4 and 8 months follow-up. Patients were randoming the area-length method. Regional wall motion was ized into two groups. The first group received intracoroanalyzed using the centerline method. nary cell therapy at baseline (early group) within 7 days Assessment of Luminal Loss by Quantitative following the MI and the second group received cells at Coronary Angiography 4 months (late group). In all patients and at al...

Viable CD34 cell count of the graft is both accurate and precise when measured on a separate sample frozen together with the cord blood unit. This measurement can be performed by the transplant center to exclude between-laboratory variability.

Background— Bone marrow CD133-postive (CD133 + ) cells possess high hematopoietic and angiogenic capacity. We tested the feasibility, safety, and functional effects of the use of enriched CD133 + progenitor cells after intracoronary administration in patients with recent myocardial infarction. Methods and Results— Among 35 patients with acute myocardial infarction treated with stenting, 19 underwent intracoronary administration of CD133 + progenitor cells (12.6±2.2×10 6 cells) 11.6±1.4 days later (group 1) and 16 did not (group 2). At 4 months, left ventricular ejection fraction increased significantly in group 1 (from 45.0±2.6% to 52.1±3.5%, P <0.05), but only tended to increase in case-matched group 2 patients (from 44.3±3.1% to 48.6±3.6%, P =NS). Likewise, left ventricular regional chordae shortening increased in group 1 (from 11.5±1.0% to 16.1±1.3%, P <0.05) but remained unchanged in group 2 patients (from 11.1±1.1% to 12.7±1.3%, P =NS). This was paralleled by reduction in the perfusion defect in group 1 (from 28.0±4.1% to 22.5±4.1%, P <0.05) and no change in group 2 (from 25.0±3.0% to 22.6±4.1%, P =NS). In group 1, two patients developed in-stent reocclusion, 7 developed in-stent restenosis, and 2 developed significant de novo lesion of the infarct-related artery. In group 2, four patients showed in-stent restenosis. In group 1 patients without reocclusion, glucose uptake shown by positron emission tomography with 18 fluorodeoxyglucose in the infarct-related territory increased from 51.2±2.6% to 57.5±3.5% ( P <0.05). No stem cell-related arrhythmias were noted, either clinically or during programmed stimulation studies at 4 months. Conclusion— In patients with recent myocardial infarction, intracoronary administration of enriched CD133 + cells is feasible but was associated with increased incidence of coronary events. Nevertheless, it seems to be associated with improved left ventricular performance paralleled with increased myocardial perfusion and viability.

REFERENCE 1. Chiaroni J, Legrand D, Dettori I, Ferrera V. Analysis of ABO discrepancies occurring in 35 French hospitals. Transfusion