title: Laser-supported CD133+ cell therapy in patients with ischemic cardiomyopathy: initial results from a prospective phase I multicenter trial.
abstract: OBJECTIVE
  This study evaluates the safety, principal feasibility and restoration potential of laser-supported CD133+ intramyocardial cell transplantation in patients with ischemic cardiomyopathy.
  
  
  METHODS
  Forty-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.
  
  
  RESULTS
  Intraoperative 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).
  
  
  CONCLUSIONS
  This 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.
  
  
  BACKGROUND
  EudraCT 2005-004051-35) Controlled-Trials.com ISRCTN49998633.
authors.affiliation: Department of Cardiovascular Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany; Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany; Center for Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Assmann
authors.affiliation: Department of Cardiovascular Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany; Research Group for Experimental Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Heke
authors.affiliation: Department of Diagnostic and Interventional Radiology, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Patric
authors.initials: P
authors.lastname: Kröpil
authors.affiliation: Department of Cardiovascular Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Ptok
authors.affiliation: Institute of Pharmacology and Clinical Pharmacology, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Hafner
authors.affiliation: Coordination Centre for Clinical Trials, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Ohmann
authors.affiliation: Clinic for Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Martens
authors.affiliation: Department of Cardiac and Thoracic Vascular Surgery, University Hospital of Schleswig-Holstein, Luebeck, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Karluβ
authors.affiliation: Clinic for Cardiac and Vascular Surgery, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Maximilian Y
authors.initials: MY
authors.lastname: Emmert
authors.affiliation: Clinic for Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Kutschka
authors.affiliation: Department of Cardiac and Thoracic Vascular Surgery, University Hospital of Schleswig-Holstein, Luebeck, Germany.
authors.forename: Hans-Hinrich
authors.initials: HH
authors.lastname: Sievers
authors.affiliation: Department of Cardiovascular Surgery, Heinrich Heine University, Medical Faculty, Duesseldorf, Germany.
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Klein
mesh_terms: D000071916:AC133 Antigen; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000378:metabolism*; D009202:Cardiomyopathies / Q000150:complications*; D002469:Cell Separation; D017690:Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D001026:Coronary Artery Bypass; D005240:Feasibility Studies; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D053685:Laser Therapy; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications* / Q000503:physiopathology / Q000628:therapy*; D010455:Peptides / Q000378:metabolism*; D012449:Safety; D016277:Ventricular Function, Left
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides