Abstract
Purpose
Infusion of a source of endothelial progenitor cells (EPC) into the ischemic myocardium is emerging as a promising therapy for coronary ischemia, probably mediated by the formation of new blood vessels. Studies have shown that while the procedure is safe and feasible, efficacy results are contentious. The investigators hypothesized that the infusion of a combination cell product consisting of a source of EPC and mesenchymal stem cells (MSC) is safe and promotes the formation of more stable and mature blood vessels resulting in improved clinical outcomes.
Methods
Ten patients with stable angina pectoris (class III to IV) on maximal medical therapy were included. All patients had ≥70% stenosis in at least one coronary artery, and none was considered a candidate for percutaneous coronary intervention or coronary artery bypass graft. End points were feasibility and safety of intracoronary infusion of the combination cell product and assessment of myocardial ischemia, left ventricular ejection fraction (LVEF), and quality of life at 6 months postinfusion.
Results
Six months after cell infusion there were no adverse clinical events. Functional cardiac evaluation during the same period showed significant improvements in LVEF (average increase: 11%, P =.02) and myocardial ischemia (average decrease: 1.8 fold, P =.02). Additionally, all patients described significant improvements in quality of life.
Conclusions
Despite the inherent limitations associated with a Phase I clinical trial, this study demonstrates that the intracoronary infusion of the combination cell product is feasible and safe and also insinuates that this form of therapy may be beneficial.
1
Introduction
Coronary atherosclerotic disease is the leading cause of chronic myocardial ischemia (CMI) and the most common cause of death in the United States and other Western societies. The traditional treatment for this condition consists of medical therapy in combination with surgical or percutaneous revascularization in selective patients. However, an important proportion of patients remain symptomatic despite optimal anti-ischemic therapy. Often these patients are considered poor candidates for revascularization therapy due to severe comorbidities and/or unsuitability of the coronary anatomy . In recent years, new therapeutic modalities using growth factors and/or stem cells have been developed to attempt to decrease myocardial ischemia and offer these patients a better quality of life and possibly to decrease the risk of cardiovascular events .
Since 2001, several clinical studies have been initiated to determine the safety and effectiveness of myocardial infusion of bone marrow- or blood-derived mononuclear cells (MNC) in patients with severe coronary artery disease, refractory stable angina pectoris, or advanced ischemic heart failure .
The common rationale of these studies is that the infusion of bone marrow- or peripheral blood-derived MNC, a source of endothelial progenitor cells (EPC), may enhance angiogenesis and promote myocardial repair . However, the formation of new mature blood vessel requires, in addition to EPC, the coordinated participation of mural cells (vascular smooth cells, pericytes) as well as the availability of local/distant growth factors, chemokines, and extracellular matrix molecules .
Bone marrow-derived mesenchymal stem cells (MSC) represent a source of pericyte progenitors and also of angiogenic growth factors and extracellular matrix components . We hypothesize that the use of a combination cellular product containing MNC as well as MSC will have a positive impact in the formation of new and stable blood vessels. The present Phase I study was designed to investigate the safety and feasibility of intracoronary infusion of a combination cell product containing autologous bone marrow-derived MNC and MSC to patients with CMI.
2
Methods
2.1
Patient population
A total of 10 patients with stable myocardial ischemia, angina functional class III or IV (Canadian Cardiovascular Society), were prospectively enrolled in the present investigation. The baseline clinical characteristics of the patient population are indicated in Table 1 . All patients had reversible perfusion defects on pharmacological single-photon emission computed tomography (SPECT). Patients with recent (≤4 weeks) acute, ST- or non-ST-elevation, myocardial infarction (MI) were excluded. All patients were enrolled at one center from February 2008 to July 2008.
