Laser-supported CD133+ cell therapy in patients with ischemic cardiomyopathy: initial results from a prospective phase I multicenter trial

PLoS One. 2014 Jul 7;9(7):e101449. doi: 10.1371/journal.pone.0101449. eCollection 2014.

Abstract

Objectives: 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.

Trial registration: EudraCT 2005-004051-35) Controlled-Trials.com ISRCTN49998633.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Aged
  • Antigens, CD / metabolism*
  • Bone Marrow Cells / metabolism*
  • Cardiomyopathies / complications*
  • Cell Separation
  • Cell Transplantation / adverse effects
  • Cell Transplantation / methods*
  • Coronary Artery Bypass
  • Feasibility Studies
  • Female
  • Glycoproteins / metabolism*
  • Humans
  • Laser Therapy*
  • Male
  • Myocardial Ischemia / complications*
  • Myocardial Ischemia / physiopathology
  • Myocardial Ischemia / therapy*
  • Peptides / metabolism*
  • Safety
  • Ventricular Function, Left

Substances

  • AC133 Antigen
  • Antigens, CD
  • Glycoproteins
  • PROM1 protein, human
  • Peptides

Associated data

  • EudraCT/2005-004051-35
  • ISRCTN/ISRCTN49998633

Grants and funding

This work was supported by the study sponsors PLC Medical Systems Inc. (Milford, USA) and Miltenyi Biotech Inc. (Bergisch Gladbach, Germany). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Moreover, this funding situation does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.