Intracoronary Autologous CD34+ Stem Cell Therapy for Intractable Angina

Abstract

Background/Objectives: A large number of patients with coronary artery disease experience angina that is not suitable for revascularization and is refractory to conventional medical therapy. Laboratory and preclinical studies have provided evidence for the safety and potential efficacy of autologous CD34+ stem cell therapies as treatment for angina. Clinical studies investigating intramyocardial transplantation of autologous CD34+ stem cells by catheter injection for patients with refractory angina show that this is safe and feasible. It remains unclear whether intracoronary infusion of CD34+ stem cells exerts beneficial effects in patients with angina as well. We addressed this question with a controlled clinical trial by enrolling 112 patients with refractory angina. Previous trials have investigated the safety and beneficial effects of CD34+ cells isolated from granulocyte colony-stimulating factor-mobilized peripheral blood; in our trial, we isolated CD34+ cells directly from the patient’s bone marrow. Methods: One hundred and twelve patients with diffuse triple-vessel disease and Canadian Cardiovascular Society class III or IV angina were enrolled in a double-blind, randomized (1:1), placebo-controlled study. Patients received optimal medical treatment but were not candidates for mechanical revascularization (percutaneous coronary intervention or coronary artery bypass grafting). Fifty-six patients (27 women and 29 men aged 42–80 years) were enrolled in the treatment group, and 56 patients (28 women and 28 men aged 43–80 years) who received optimal medical treatment and intracoronary saline injections were enrolled in the placebo control group. Bone marrow was collected from all enrolled patients at a volume of 120–150 ml each in both groups. Selections of CD34+ cells were performed by a CE-marked device approved by the Security, Food and Drug Administration of China. Coronary angiography had been performed before enrollment in this study. Results: No myocardial infarction was observed during intracoronary infusion. The intracoronary infusion of cells or saline did not result in cardiac enzyme elevation, cardiac perforation or pericardial effusion. No arrhythmia, such as ventricular tachycardia or ventricular fibrillation, was induced by intracoronary infusion. No serious adverse events occurred in either group. The reduction in the frequency of angina episodes per week 3 and 6 months after infusion was significantly higher in the treatment group (–14.6 ± 4.8 at 3 months and –15.6 ± 4.0 at 6 months) than in the control group (–4.5 ± 0.3 and –3.0 ± 1.2, respectively; p < 0.01). Other efficacy parameters such as nitroglycerine usage, exercise time and the Canadian Cardiovascular Society class also showed an improvement in the treatment group compared to the control group. A significant improvement in myocardial perfusion was noted in the treatment group compared to the control group, as measured by single-photon emission computed tomography. Conclusions: This randomized trial investigating intracoronary infusi...

Impact of Cell Therapy on Myocardial Perfusion and Cardiovascular Outcomes in Patients With Angina Refractory to Medical Therapy

“…There was no allocation bias, since adequate randomization was reported in all of the trials except two. 14, 17 All assessments of outcomes measured were blinded, with a low risk of documented bias both for selection and for reported outcomes. The RCTs included in the analysis had a low risk of bias due to attrition during follow-up.…”

Detailed Analysis of Bone Marrow From Patients With Ischemic Heart Disease and Left Ventricular Dysfunction

“…Leading up to this report, Losordo et al and Wang et al demonstrated reduced frequency of angina pectoris and improved exercise tolerance in IHD patients who received intramyocardial and intracoronary injections of autologous CD34+ cells compared to placebo. 9, 25, 26 In patients with nonischemic dilated cardiomyopathy, transendocardial injection of autologous CD34+ cells was associate with higher myocardial retention rates and greater improvements in ventricular function compared to intracoronary route. 27 Our data confirm the importance of CD34 number in BMC mediated repair after AMI but go on to show that even when cell number is intact, progenitor cell function can be decreased in these patients – reinforcing the concept that reversal of loss of function may be equally as important as improving cell number.…”

Improvement in Cardiac Function following Transplantation of Human Umbilical Cord Matrix-Derived Mesenchymal Cells

“…In addition to bone marrow as a common source of mesenchymal cells [8], multipotent MSC can be collected from extraembryonic tissues including placental and umbilical cord blood (UCB) [9] as well as umbilical cord matrix (UCM) [10], which needs to be given more attention. Studies have indicated the feasibility of MSCs derived from extraembryonic tissues [11], including UCB cells for the repair of ischemic heart diseases [12,13,14].…”