Randomized, double-blind pilot study of transendocardial injection of autologous aldehyde dehydrogenase-bright stem cells in patients with ischemic heart failure

Am Heart J. 2012 Mar;163(3):415-21, 421.e1. doi: 10.1016/j.ahj.2011.11.020. Epub 2012 Feb 10.

Abstract

Background: The optimal type of stem cell for use in patients with ischemic heart disease has not been determined. A primitive population of bone marrow-derived hematopoietic cells has been isolated by the presence of the enzyme aldehyde dehydrogenase and comprises a multilineage mix of stem and progenitor cells. Aldehyde dehydrogenase-bright (ALDH(br)) cells have shown promise in promoting angiogenesis and providing perfusion benefits in preclinical ischemia studies. We hypothesize that ALDH(br) cells may be beneficial in treating ischemic heart disease and thus conducted the first randomized, controlled, double-blind study to assess the safety of the transendocardial injection of autologous ALDH(br) cells isolated from the bone marrow in patients with advanced ischemic heart failure.

Methods: Aldehyde dehydrogenase-bright cells were isolated from patients' bone marrow on the basis of the expression of a functional (aldehyde dehydrogenase) marker. We enrolled 20 patients (treatment, n = 10; control, n = 10). Safety (primary end point) and efficacy (secondary end point) were assessed at 6 months.

Results: No major adverse cardiovascular or cerebrovascular events occurred in ALDH(br)-treated patients in the periprocedural period (up to 1 month); electromechanical mapping-related ventricular tachycardia (n = 2) and fibrillation (n = 1) occurred in control patients. Aldehyde dehydrogenase-bright-treated patients showed a significant decrease in left ventricular end-systolic volume at 6 months (P = .04) and a trend toward improved maximal oxygen consumption. The single photon emission computed tomography delta analysis showed a trend toward significant improvement in reversibility in cell-treated patients (P = .053).

Conclusions: We provide preliminary evidence that treatment with the novel cell population, ALDH(br) cells, is safe and may provide perfusion and functional benefits in patients with chronic myocardial ischemia.

Publication types

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

MeSH terms

  • Aldehyde Dehydrogenase / pharmacology*
  • Body Surface Potential Mapping
  • Double-Blind Method
  • Endocardium
  • Female
  • Follow-Up Studies
  • Heart Failure / complications
  • Heart Failure / diagnosis
  • Heart Failure / therapy*
  • Humans
  • Injections
  • Male
  • Middle Aged
  • Myocardial Ischemia / complications
  • Myocardial Ischemia / diagnosis
  • Myocardial Ischemia / therapy*
  • Pilot Projects
  • Stem Cell Transplantation / methods*
  • Tomography, Emission-Computed, Single-Photon
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Aldehyde Dehydrogenase