Selected CD133⁺ progenitor cells to promote angiogenesis in patients with refractory angina: final results of the PROGENITOR randomized trial

Circ Res. 2014 Nov 7;115(11):950-60. doi: 10.1161/CIRCRESAHA.115.303463. Epub 2014 Sep 17.

Abstract

Rationale: Refractory angina constitutes a clinical problem.

Objective: The aim of this study was to assess the safety and the feasibility of transendocardial injection of CD133(+) cells to foster angiogenesis in patients with refractory angina.

Methods and results: In this randomized, double-blinded, multicenter controlled trial, eligible patients were treated with granulocyte colony-stimulating factor, underwent an apheresis and electromechanical mapping, and were randomized to receive treatment with CD133(+) cells or no treatment. The primary end point was the safety of transendocardial injection of CD133(+) cells, as measured by the occurrence of major adverse cardiac and cerebrovascular event at 6 months. Secondary end points analyzed the efficacy. Twenty-eight patients were included (n=19 treatment; n=9 control). At 6 months, 1 patient in each group had ventricular fibrillation and 1 patient in each group died. One patient (treatment group) had a cardiac tamponade during mapping. There were no significant differences between groups with respect to efficacy parameters; however, the comparison within groups showed a significant improvement in the number of angina episodes per month (median absolute difference, -8.5 [95% confidence interval, -15.0 to -4.0]) and in angina functional class in the treatment arm but not in the control group. At 6 months, only 1 simple-photon emission computed tomography (SPECT) parameter: summed score improved significantly in the treatment group at rest and at stress (median absolute difference, -1.0 [95% confidence interval, -1.9 to -0.1]) but not in the control arm.

Conclusions: Our findings support feasibility and safety of transendocardial injection of CD133(+) cells in patients with refractory angina. The promising clinical results and favorable data observed in SPECT summed score may set up the basis to test the efficacy of cell therapy in a larger randomized trial.

Keywords: angiogenesis effect; endothelial progenitor cells; myocardial ischemia; stem cells.

Publication types

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

MeSH terms

  • AC133 Antigen
  • Aged
  • Angina Pectoris / diagnostic imaging
  • Angina Pectoris / therapy*
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Double-Blind Method
  • Endothelial Progenitor Cells / cytology
  • Endothelial Progenitor Cells / metabolism
  • Endothelial Progenitor Cells / transplantation*
  • Female
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Neovascularization, Physiologic*
  • Peptides / genetics
  • Peptides / metabolism*
  • Prospective Studies
  • Stem Cell Transplantation / adverse effects
  • Stem Cell Transplantation / methods*
  • Tomography, Emission-Computed, Single-Photon

Substances

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