A randomized, controlled study of autologous therapy with bone marrow-derived aldehyde dehydrogenase bright cells in patients with critical limb ischemia

Catheter Cardiovasc Interv. 2011 Dec 1;78(7):1060-7. doi: 10.1002/ccd.23066. Epub 2011 May 18.

Abstract

Objectives: The safety and efficacy of direct intramuscular injections of aldehyde dehydrogenase bright (ALDH(br)) cells isolated from autologous bone marrow mononuclear cells (ABMMNCs) and ABMMNCs were studied in patients with critical limb ischemia (CLI) who were not eligible for percutaneous or surgical revascularization.

Background: Many CLI patients are not candidates for current revascularization procedures, and amputation rates are high in these patients. Cell therapy may be a viable option for CLI patients.

Methods: Safety was the primary objective and was evaluated by occurrence of adverse events. Efficacy, the secondary objective, was evaluated by assessment of Rutherford category, ankle-brachial index (ABI), transcutaneous partial pressure of oxygen (TcPO(2)), quality of life, and pain.

Results: ALDH(br) cells and ABMMNCs were successfully administered to all patients. No therapy-related serious adverse events occurred. Patients treated with ALDH(br) cells (n = 11) showed significant improvements in Rutherford category from baseline to 12 weeks (mean, 4.09 ± 0.30 to 3.46 ± 1.04; P = 0.05) and in ABI at 6 (mean, 0.22 ± 0.19 to 0.30 ± 0.24; P = 0.02), and 12 weeks (mean, 0.36 ± 0.18; P = 0.03) compared with baseline. Patients in the ABMMNC group (n = 10) showed no significant improvements at 6 or 12 weeks in Rutherford category but did show improvement in ABI from baseline to 12 weeks (0.38 ± 0.06 to 0.52 ± 0.16; P = 0.03). No significant changes from baseline were noted in ischemic ulcer grade or TcPO(2) in either group.

Conclusions: Administration of autologous ALDH(br) cells appears to be safe and warrants further study in patients with CLI.

Trial registration: ClinicalTrials.gov NCT00392509.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aldehyde Dehydrogenase / metabolism*
  • Ankle Brachial Index
  • Bone Marrow Cells / enzymology*
  • Bone Marrow Transplantation* / adverse effects
  • Cell Separation / methods
  • Critical Illness
  • Double-Blind Method
  • Extremities / blood supply*
  • Female
  • Flow Cytometry
  • Hemodynamics
  • Humans
  • Injections, Intramuscular
  • Ischemia / diagnosis
  • Ischemia / enzymology
  • Ischemia / physiopathology
  • Ischemia / surgery*
  • Male
  • Middle Aged
  • Recovery of Function
  • Regional Blood Flow
  • Time Factors
  • Transplantation, Autologous
  • Treatment Outcome
  • United States

Substances

  • Aldehyde Dehydrogenase

Associated data

  • ClinicalTrials.gov/NCT00392509