Fan-Yen Lee1, Yung-Lung Chen, Pei-Hsun Sung, Ming-Chun Ma, Sung-Nan Pei, Chiung-Jen Wu, Cheng-Hsu Yang, Morgan Fu, Sheung-Fat Ko, Steve Leu, Hon-Kan Yip. 1. 1Division of thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 2Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 3Division of Hema-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 4Department of Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 5Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 6Center of Shock Wave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 7Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Abstract
OBJECTIVE: This study tested the hypothesis that intra-coronary transfusion of circulation-derived autologous CD34+ cells can improve ischemia-related left ventricular dysfunction in patients with severe diffuse coronary artery disease refractory to medication and unsuitable for coronary intervention. DESIGN: A prospective, randomized, double-blinded phase I clinical trial. SETTING: Tertiary care center. PATIENTS: Thirty-eight patients with severe diffuse coronary artery disease were randomized into group 1 and group 2 receiving CD34+ cell infusion with dosages of 1.0 x 107 and 3.0 x 107 cells/vessel, respectively, after subcutaneous G-CSF injection (5 μg/kg twice a day for 4 d). INTERVENTIONS: Cardiac catheterization and intra-coronary administration of CD34+ cells. MEASUREMENTS AND MAIN RESULTS: This clinical trial was to test effectiveness and safety of these two different dosages of CD34+ cells in the setting of severe diffuse coronary artery disease. Blood samples were collected for endothelial progenitor cell culture before and after granulocyte colony-stimulating factor injection for matrigel-assay and comparison of levels of soluble angiogenesis factors (vascular endothelial growth factor, epithelial growth factor, hepatocyte growth factor, angiopoietin-1, and transforming growth factor-β). Procedural safety was 100% with all patients uneventfully discharged. The numbers of endothelial progenitor cells in blood samples from coronary sinus after transfusion were higher than those in circulation, and the circulatory level was higher after granulocyte colony-stimulating factor treatment (all p < 0.001). Cardiac MRI and three-dimensional echocardiography at 6 month and angiographic follow-up at 9 month showed improvement in left ventricular ejection fraction (p < 0.001) and consistent increase in neovascularization (p < 0.001), respectively, in both groups. Despite good correlation in angiogenesis between 9-month angiography and matrigel-assay (p < 0.001), no significant correlation was noted in of soluble angiogenesis factor levels. Angina and heart failure were improved in both groups at 12-month follow-up (all p < 0.001). The survival rate at 18.5-month follow-up was 94.7% (n = 36). CONCLUSIONS:CD34+ cell therapy was safe and efficacious in improving heart function for patients with severe diffuse coronary artery disease unsuitable for coronary intervention and with poor response to pharmacotherapy.
RCT Entities:
OBJECTIVE: This study tested the hypothesis that intra-coronary transfusion of circulation-derived autologous CD34+ cells can improve ischemia-related left ventricular dysfunction in patients with severe diffuse coronary artery disease refractory to medication and unsuitable for coronary intervention. DESIGN: A prospective, randomized, double-blinded phase I clinical trial. SETTING: Tertiary care center. PATIENTS: Thirty-eight patients with severe diffuse coronary artery disease were randomized into group 1 and group 2 receiving CD34+ cell infusion with dosages of 1.0 x 107 and 3.0 x 107 cells/vessel, respectively, after subcutaneous G-CSF injection (5 μg/kg twice a day for 4 d). INTERVENTIONS: Cardiac catheterization and intra-coronary administration of CD34+ cells. MEASUREMENTS AND MAIN RESULTS: This clinical trial was to test effectiveness and safety of these two different dosages of CD34+ cells in the setting of severe diffuse coronary artery disease. Blood samples were collected for endothelial progenitor cell culture before and after granulocyte colony-stimulating factor injection for matrigel-assay and comparison of levels of soluble angiogenesis factors (vascular endothelial growth factor, epithelial growth factor, hepatocyte growth factor, angiopoietin-1, and transforming growth factor-β). Procedural safety was 100% with all patients uneventfully discharged. The numbers of endothelial progenitor cells in blood samples from coronary sinus after transfusion were higher than those in circulation, and the circulatory level was higher after granulocyte colony-stimulating factor treatment (all p < 0.001). Cardiac MRI and three-dimensional echocardiography at 6 month and angiographic follow-up at 9 month showed improvement in left ventricular ejection fraction (p < 0.001) and consistent increase in neovascularization (p < 0.001), respectively, in both groups. Despite good correlation in angiogenesis between 9-month angiography and matrigel-assay (p < 0.001), no significant correlation was noted in of soluble angiogenesis factor levels. Angina and heart failure were improved in both groups at 12-month follow-up (all p < 0.001). The survival rate at 18.5-month follow-up was 94.7% (n = 36). CONCLUSIONS:CD34+ cell therapy was safe and efficacious in improving heart function for patients with severe diffuse coronary artery disease unsuitable for coronary intervention and with poor response to pharmacotherapy.
Authors: Mateusz Puslecki; Piotr Buczkowski; Michał Nowicki; Patrycja Sujka-Kordowska; Marcin Ligowski; Marcin Misterski; Sebastian Stefaniak; Marek Dąbrowski; Agata Dabrowska; Michal Bocianski; Lukasz Szarpak; Kurt Ruetzler; Marek Jemielity; Bartlomiej Perek Journal: J Thorac Dis Date: 2018-08 Impact factor: 2.895