Transplantation of Blood-Derived Progenitor Cells After Recanalization of Chronic Coronary Artery Occlusion

Abstract

Abstract-Transplantation of blood-derived circulating progenitor cells (CPC) has been shown to improve myocardial regeneration after myocardial infarction. It remains unclear whether CPC transplantation exerts beneficial effects also in patients with chronic myocardial ischemia. We initiated a randomized, double-blind, placebo-controlled study evaluating the impact of intracoronary infusion of CPCs on coronary vasomotion and left ventricular (LV) function in patients after recanalization of chronic coronary total occlusion (CTO). After recanalization of CTO, 26 patients (age, 63Ϯ2 years; LV ejection fraction, 53Ϯ2%) were randomly assigned to the treatment (intracoronary transplantation of CPCs) or control group. Coronary flow reserve in response to adenosine (2.4 mg/min) was measured in the target vessel at the beginning of the study and after 3 months. LV function and infarct size were assessed by MRI and metabolism by 18 F deoxyglucose positron emission tomography. CPC application resulted in an increase in coronary flow reserve by 43% from 2.3Ϯ0.3 to 3.3Ϯ0.5 (PϽ0.05 versus beginning and control). At 3 months, the number of hibernating segments in the target region (from 2.9Ϯ0.6 to 2.0Ϯ0.6 segments, PϽ0.05 versus beginning and control) had declined in the treatment group, whereas no significant changes were observed in the control group. MRI revealed a reduction in infarct size by 16% and an increase in LV ejection fraction by 14% in the treatment group (from 51.7Ϯ3.7 to 58.9Ϯ3.2%; PϽ0.05 versus beginning and control) because of an augmented wall motion in the target region. Hence, intracoronary transplantation of CPCs after recanalization of CTO results in an improvement of macro-and microvascular function and contributes to the recruitment of hibernating myocardium. Key Words: ischemic heart disease Ⅲ endothelial dysfunction Ⅲ progenitor cells Ⅲ hibernating myocardium Ⅲ reperfusion R ecently, bone marrow-derived circulating progenitor cells (CPCs) have been shown to promote formation of entirely new vessels into ischemic tissues by a process termed vasculogenesis. 1-3 The CPC-mediated augmentation in myocardial neoangiogenesis in animal experiments prompted researchers to conduct pioneer clinical trials. [3][4][5][6][7][8][9][10] In the TOPCARE-AMI (Transplantation Of Progenitor Cells And Regeneration Enhancement in Acute Myocardial Infarction) study, bone marrow-derived and progenitor cells from peripheral blood administered after successful recanalization in acute myocardial infarction were shown to improve myocardial perfusion, increase left ventricular (LV) contractility, and attenuate LV remodeling equally effective. 9 Perin et al were able to extend the knowledge with regard to bone marrowderived stem cell therapy in patients with severe ischemic heart failure: intramyocardial injection of these cells at the site of ischemia was elucidated to increase blood flow and improve regional and global ventricular function. 5 Additional evidence is emerging from the first randomized study, BOOST (BOne marrOw tr...

Endothelial progenitor cells: Implications for cardiovascular disease

“…Schots et al demonstrated using labeled stem cells that these cells are capable of homing (117), and a small randomized study showed that this therapy is effective in improving the movement of the former infracted region. A larger randomized study by Erbs et al (118) dealt with chronic total occlusions ([3 months) after myocardial infarction. This study showed after successful recanalization of the occluded vessel and afterwards randomization into a stem cell therapy group or a control group, a reduction in hibernating myocardial segments by 31% for the stem cell group whereas no change was found in the control group.…”

“…Furthermore, global LV-ejection fraction was significantly increased by 7.2% at the stem cell group after 3 months compared with no change in the control group. A possible pathophysiological explanation for the beneficial effect of the stem cell treatment may be the resulted increase in coronary flow reserve by 43% after 3 months compared with the placebo group (118).…”

Stem Cell Therapy for Heart Disease

“…43,53,54,62 Heart Failure Additionally, there have been multiple HF trials (Table 2). Many demonstrated benefits in ventricular function noted by increased EF, [68][69][70][71][72][73]75,79,82,83 improved functional class, 75,78,80,82,83,86 reduced infarct size, 70,72,80,[82][83][84] decreased mortality, 79 and acceptable safety outcomes. [66][67][68][69]75,78,80,[82][83][84]86 SCIPIO was the first trial using autologous CSC in HF and showed improvement in EF, infarct size, viable tissue, and HF scores.…”

Adult bone marrow–derived stem cells for organ regeneration and repair

“…MNC preparations contain mainly different stages of progenitor cells and true HSCs and MSCs are rare in these autografts. Smaller studies established the safety of this approach and demonstrated functional and metabolic regeneration of myocardial tissue (Strauer et al, 2005), improvement of vascular function (Erbs et al, 2005), global left ventricular performance (Stamm et al, 2003;Fernandez-Aviles et al, 2004), and peripheral vascular disease (TateishiYuyama et al, 2002). Based on these promising results, larger randomized multicenter trials were conducted.…”