Correlation between Therapeutic Efficacy of CD34(+) Cell Treatment and Directed In Vivo Angiogenesis in Patients with End-Stage Diffuse Coronary Artery Disease

BACKGROUND: This study was aimed at testing the association between the therapeutic efficacy of CD34(+) cell treatment in patients with end-stage diffuse coronary artery disease as reflected in angiographic grading and results of directed in vivo angiogenesis assay (DIVAA) on their isolated peripheral blood mononuclear cell- (PBMC-) derived endothelial progenitor cells (EPCs). METHODS: Angiographic grades (0: <5%; 1: 5–35%; 2: 35–75%; 3: >75%) which presented the improvement of vessel density pre- and post-CD34(+) treatment were given to 30 patients with end-stage diffuse coronary artery disease having received CD34(+) cell treatment. The patients were categorized into low-score group (angiographic grade 0 or 1, n = 12) and high-score group (angiographic grade 2 or 3, n = 18). The percentages of circulating EPCs with KDR(+)/CD34(+)/CD45(−), CD133(+)/CD34(+)/CD45(−), and CD34(+) were determined in each patient using flow cytometry. PBMC-derived EPCs from all patients were subjected to DIVAA through a 14-day implantation in nude mice. The DIVAA ratio (i.e., mean fluorescent units in angioreactors with EPCs/mean fluorescent units in angioreactors without EPCs) was obtained for each animal with implanted EPCs from each patient. RESULTS AND CONCLUSIONS: The number of EPCs showed no significant difference among the two groups. The DIVAA ratio in the high-score group was significantly higher than that in the low-score group (p = 0.0178). Logistic regression revealed a significant association between the DIVAA ratio and angiographic grading (OR 3.12, 95% CI: 1.14–8.55, p = 0.027). The area under the ROC curve (AUC) was 0.8519 (p = 0.0013). We proposed that DIVAA may be a reliable tool for assessing coronary vascularization after CD34(+) cell treatment.