Intracoronary Transfusion of Circulation-Derived CD34+ Cells Improves Left Ventricular Function in Patients With End-Stage Diffuse Coronary Artery Disease Unsuitable for Coronary Intervention*

Abstract

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.

Investigated the safety of intra-renal arterial transfusion of autologous CD34+ cells and time courses of creatinine levels, endothelial dysfunction biomarkers and micro-RNAs in chronic kidney disease patients-phase I clinical trial

“…These findings highlighted that not only the number of EPCs in circulation but also integrity of the endothelial function and capacity of endothelial-cell repairmen/renew were substantially weakened in CKD patients. Interestingly, our recent study has shown that the circulating levels of EPCs and the angiogenesis ability in both in-vitro and angiographic studies were significantly reduced in patients with diffuse coronary artery disease (CAD) [39]. Therefore, the conclusions reached in our recent study [39] corroborated the findings in the present study.…”

“…Interestingly, our recent study has shown that the circulating levels of EPCs and the angiogenesis ability in both in-vitro and angiographic studies were significantly reduced in patients with diffuse coronary artery disease (CAD) [39]. Therefore, the conclusions reached in our recent study [39] corroborated the findings in the present study. Importantly, the finding of our recent study [39] demonstrated that peripheral blood-derived CD34+ cell therapy significantly improved angina, heart failure and left ventricular function, supporting our hypothesis that CD34+ cell therapy might be beneficial to CKD patients with endothelial cell dysfunction.…”

“…On the other hand, numerous experimental studies have shown that stem cell therapy improves ischemia-induced organ dysfunction through angiogenesis and restoring blood flow in the ischemic area [35–37]. Additionally, growing data from clinical trials [38], including our recent study [39], have shown that both circulatory derived and bone marrow derived CD34+ stem cell therapy remarkably improved angina and ischemia-related left ventricular dysfunction, and restored the microvascular blood flow.…”

“…The results of our animal model study [37] and clinical trial [39] encouraged the use of circulatory-derived autologous stem cell therapy for patients with CKD. Accordingly, a phase I clinical trial employing autologous CD34+ cell to treated patients with CKD stages III and IV was performed with two essential purposes as: (1) to investigate the safety of autologous administration of peripheral blood-derived CD34+ cells to CKD patients, and (2) to analyze endothelial dysfunction elements, focusing on the angiogenesis (i.e., by Matrigel assay) and circulating anti-apoptotic micro-RNAs.…”

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

“…Clinical trials using G-CSF mobilized stem and progenitor cells have led to inconsistent data. Several studies showed significant therapeutic effects after intramyocardial or intracoronary injection of PB-derived MNCs [131-134] and CD34 + [135][136][137][138][139][140][141][142][143][144], whereas others did not detect functional differences between SC-treated and control groups [72,145,146]. Nevertheless, recently published data suggested that low circulating stem and progenitor cell counts are associated with minor heart function improvement after MI [99] and contribute to the development and progression of heart failure (HF) [147].…”