A randomized, controlled pilot study of autologous CD34+ cell therapy for critical limb ischemia

Douglas W. Losordo*, Melina R. Kibbe, Farrell Mendelsohn, William Marston, Vickie R. Driver, Melhem Sharafuddin, Victoria Teodorescu, Bret N. Wiechmann, Charles Thompson, Larry Kraiss, Teresa Carman, Suhail Dohad, Paul Huang, Candice E. Junge, Kenneth Story, Tara Weistroffer, Tina M. Thorne, Meredith Millay, John Paul Runyon, Robert Schainfeld

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

Background-Critical limb ischemia portends a risk of major amputation of 25% to 35% within 1 year of diagnosis. Preclinical studies provide evidence that intramuscular injection of autologous CD34+ cells improves limb perfusion and reduces amputation risk. In this randomized, double-blind, placebo-controlled pilot study, we evaluated the safety and efficacy of intramuscular injections of autologous CD34+ cells in subjects with moderate or high-risk critical limb ischemia, who were poor or noncandidates for surgical or percutaneous revascularization (ACT34-CLI). Methods and Results-Twenty-eight critical limb ischemia subjects were randomized and treated: 7 to 1×105 (low-dose) and 9 to 1×106 (high-dose) autologous CD34+ cells/kg; and 12 to placebo (control). Intramuscular injections were distributed into 8 sites within the ischemic lower extremity. At 6 months postinjection, 67% of control subjects experienced a major or minor amputation versus 43% of low-dose and 22% of high-dose cell-treated subjects (P=0.137). This trend continued at 12 months, with 75% of control subjects experiencing any amputation versus 43% of low-dose and 22% of high-dose cell-treated subjects (P=0.058). Amputation incidence was lower in the combined cell-treated groups compared with control group (6 months: P=0.125; 12 months: P=0.054), with the low-dose and high-dose groups individually showing trends toward improved amputation-free survival at 6 months and 12 months. No adverse safety signal was associated with cell administration. Conclusions-This study provides evidence that intramuscular administration of autologous CD34+ cells was safe in this patient population. Favorable trends toward reduced amputation rates in cell-treated versus control subjects were observed. These findings warrant further exploration in later-phase clinical trials.

Original languageEnglish (US)
Pages (from-to)821-830
Number of pages10
JournalCirculation: Cardiovascular Interventions
Volume5
Issue number6
DOIs
StatePublished - Dec 2012

Keywords

  • Peripheral vascular disease
  • Randomized trial
  • Reperfusion
  • Revascularization
  • Stem cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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