Laser-Supported CD133+ Cell Therapy in Patients with Ischemic Cardiomyopathy: Initial Results from a Prospective Phase I Multicenter Trial

Abstract

ObjectivesThis study evaluates the safety, principal feasibility and restoration potential of laser-supported CD133+ intramyocardial cell transplantation in patients with ischemic cardiomyopathy.MethodsForty-two patients with severe ischemic cardiomyopathy (left ventricular ejection fraction (LVEF) >15% and <35%) were included in this prospective multicenter phase I trial. They underwent coronary artery bypass grafting (CABG) with subsequent transepicardial low-energy laser treatment and autologous CD133+ cell transplantation, and were followed up for 12 months. To evaluate segmental myocardial contractility as well as perfusion and to identify the areas of scar tissue, cardiac MRI was performed at 6 months and compared to the preoperative baseline. In addition, clinical assessment comprising of CCS scoring, blood and physical examination was performed at 3, 6 and 12 months, respectively.ResultsIntraoperative cell isolation resulted in a mean cell count of 9.7±1.2×106. Laser treatment and subsequent CD133+ cell therapy were successfully and safely carried out in all patients and no procedure-related complications occurred. At 6 months, the LVEF was significantly increased (29.7±1.9% versus 24.6±1.5% with p = 0.004). In addition, freedom from angina was achieved, and quality of life significantly improved after therapy (p<0.0001). Interestingly, an extended area of transmural delayed enhancement (>3 myocardial segments) determined in the preoperative MRI was inversely correlated with a LVEF increase after laser-supported cell therapy (p = 0.024).ConclusionsThis multicenter trial demonstrates that laser-supported CD133+ cell transplantation is safe and feasible in patients with ischemic cardiomyopathy undergoing CABG, and in most cases, it appears to significantly improve the myocardial function. Importantly, our data show that the beneficial effect was significantly related to the extent of transmural delayed enhancement, suggesting that MRI-guided selection of patients is mandatory to ensure the effectiveness of the therapy.Trial Registration:EudraCT 2005-004051-35) Controlled-Trials.com ISRCTN49998633

Intraportal Infusion of Bone Marrow Mononuclear or CD133+ Cells in Patients With Decompensated Cirrhosis: A Double-Blind Randomized Controlled Trial

“…Furthermore, intraportal injection of autologous CD133 + cells expanded the remaining hepatic segments after hepatectomy and resulted in a 2.5‐fold increase in mean proliferation rates of the segments compared with the placebo groups [18]. CD133 + cells have also been studied in other inflammatory conditions such as ischemic cardiomyopathy [24, 25]. Although the mechanism of action of CD133 + cells in tissue regeneration is not well understood, it seems they exert a partial effect via their proangiogenic properties [26, 27].…”

Autologous CD133 + Cells and Laser Revascularization in patients with severe Ischemic Cardiomyopathy

“…On the day of the procedure, patients underwent bone marrow aspiration and CD133 + cells were processed and separated using the clinical-grade closed CliniMACS system (Miltenyi Biotech, Germany) 7 .…”

Regenerative Capacity of Autologous Stem Cell Transplantation in Elderly: A Report of Biomedical Outcomes

“…Several clinical trials have been performed on ischemic and nonischemic cardiomyopathies in patients greater than 50 years old. The most promising among those trials included intracoronary infusion of mononuclear fractions of bone marrow-derived stem cells or MSCs from peripheral blood in patients suffering a myocardial infarction, in whom a moderate but significant improvement in left ventricular ejection volume was observed [65][66][67][68][69][70][71][72]. Transplantation of the specific stem cell fraction bearing CD133 + , CD34 + or both antigens improves the quality of life after cell therapy in all cases [50,73,74].…”