CABG And Intramyocardial Delivery Of Purified CD133+ Bone Marrow Stem Cells: Final Phase-1 And Phase-2 Results
Back to 86th Annual Meeting
Back to Program Outline
Objective: We tested the hypothesis that intramyocardial delivery of autologous CD133+ bone marrow cells in conjunction with CABG surgery improves left ventricular function more than CABG alone.
Methods: A total of 55 patients with triple vessel disease with impaired left ventricular contractility were enrolled in the trial between 2001 and 2005. The first 15 patients took part in a phase-1 safety evaluation, and the subsequent 40 patients were randomized to undergo CABG and CD133+ cell injection or CABG alone. Bone marrow was harvested from the iliac crest one day prior to surgery, and up to 80x10E6 CD133+ progenitor cells were isolated using magnetic bead-conjugated antibody. LV function was measured by echocardiography and myocardial perfusion by SPECT. More recently, cardiac MRI was used to confirm the echocardiographic data.
Results: In the phase-1 safety trial, there was no evidence of new ventricular arrhythmia or neoplasia within >500 patient months. One patient died 9 months postoperatively due to a stroke. LVEF increased from 39±9% to 47±6% at 2 weeks (p=0.004) and 50±8% at 6 months (p=0.0007), and LVEDV decreased from 148±38% to 123±32% (p=0.01) and 125±28% (p=0.05, all paired t-test). In the controlled phase-2 trial, LVEF increased from 37±8% to 40±11% at 2 weeks (p=0.5) and 47±8% at 6 months (p=0.0001) in cell-treated CABG patients, and from 39±10% to 41±10% at 2 weeks (p=0.05) and 41±9% at 6 months (p=0.01, all paired t-test) in CABG-only control patients. Comparing both groups statistically (unpaired t-test), the mean LVEF was not different at 2 weeks postop. (p=0.7) but significantly higher in the cell-treated group at 6 months (p=0.04). The increase in LVEF over 6 months was also significantly higher in cell-treated patients (p=0.009). Similarly, perfusion in the cell-treated myocardium at 6 months was better than in the corresponding area in control patients. Regression analysis indicated that patients with preoperative LVEF <30% benefit more from CABG and cell therapy than those with only moderately impaired LVEF.
Conclusions: Although the additional increase in contractility is modest, CABG & CD133+ bone marrow cell results in better medium-term LV function than CABG alone.
Back to 86th Annual Meeting
Back to Program Outline
