Safety and effect of adipose tissue-derived stem cell implantation in patients with critical limb ischemia: a pilot study

Circ J. 2012;76(7):1750-60. doi: 10.1253/circj.cj-11-1135. Epub 2012 Apr 12.

Abstract

Background: Treatment of critical limb ischemia (CLI) by bypass operation or percutaneous vascular intervention is occasionally difficult. The safety and efficacy of multiple intramuscular adipose tissue-derived mesenchymal stem cells (ATMSC) injections in CLI patients was determined in the study.

Methods and results: The study included 15 male CLI patients with ischemic resting pain in 1 limb with/without non-healing ulcers and necrotic foot. ATMSC were isolated from adipose tissue of thromboangiitis obliterans (TAO) patients (B-ATMSC), diabetes patients (D-ATMSC), and healthy donors (control ATMSC). In a colony-forming unit assay, the stromal vascular fraction of TAO and diabetic patients yielded lesser colonies than that of healthy donors. D-ATMSC showed lower proliferation abilitythan B-ATMSC and control ATMSC, but they showed similar angiogenic factor expression with control ATMSC and B-ATMSC. Multiple intramuscular ATMSC injections cause no complications during the follow-up period (mean follow-up time: 6 months). Clinical improvement occurred in 66.7% of patients. Five patients required minor amputation during follow-up, and all amputation sites healed completely. At 6 months, significant improvement was noted on pain rating scales and in claudication walking distance. Digital subtraction angiography before and 6 months after ATMSC implantation showed formation of numerous vascular collateral networks across affected arteries.

Conclusions: Multiple intramuscular ATMSC injections might be a safe alternative to achieve therapeutic angiogenesis in patients with CLI who are refractory to other treatment modalities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Adult
  • Aged
  • Amputation
  • Angiography, Digital Subtraction
  • Cells, Cultured
  • Collateral Circulation
  • Critical Illness
  • Diabetic Foot / surgery
  • Exercise Tolerance
  • Humans
  • Injections, Intramuscular
  • Intermittent Claudication / diagnostic imaging
  • Intermittent Claudication / physiopathology
  • Intermittent Claudication / surgery*
  • Ischemia / diagnostic imaging
  • Ischemia / physiopathology
  • Ischemia / surgery*
  • Leg Ulcer / diagnostic imaging
  • Leg Ulcer / physiopathology
  • Leg Ulcer / surgery*
  • Limb Salvage
  • Lower Extremity / blood supply*
  • Male
  • Mesenchymal Stem Cell Transplantation* / adverse effects
  • Middle Aged
  • Neovascularization, Physiologic
  • Pilot Projects
  • Recovery of Function
  • Regional Blood Flow
  • Reoperation
  • Republic of Korea
  • Time Factors
  • Treatment Outcome
  • Walking
  • Wound Healing
  • Young Adult