title: Safety and effect of adipose tissue-derived stem cell implantation in patients with critical limb ischemia: a pilot study.
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.
  
  
  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.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Pusan National University, Medical Research Institute, Pusan Medical University Hospital, Busan, Korea.
authors.forename: Han Cheol
authors.initials: HC
authors.lastname: Lee
authors.forename: Sung Gyu
authors.initials: SG
authors.lastname: An
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Lee
authors.forename: Jin-Sup
authors.initials: JS
authors.lastname: Park
authors.forename: Kwang Soo
authors.initials: KS
authors.lastname: Cha
authors.forename: Taek Jong
authors.initials: TJ
authors.lastname: Hong
authors.forename: Jong Ha
authors.initials: JH
authors.lastname: Park
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Sang-Pil
authors.initials: SP
authors.lastname: Kim
authors.forename: Yeong Dae
authors.initials: YD
authors.lastname: Kim
authors.forename: Sung Woon
authors.initials: SW
authors.lastname: Chung
authors.forename: Yong Chan
authors.initials: YC
authors.lastname: Bae
authors.forename: Yong Beom
authors.initials: YB
authors.lastname: Shin
authors.forename: Jeung Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Jin Sup
authors.initials: JS
authors.lastname: Jung
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000368:Aged; D000671:Amputation, Surgical; D015901:Angiography, Digital Subtraction; D002478:Cells, Cultured; D003097:Collateral Circulation; D016638:Critical Illness; D017719:Diabetic Foot / Q000601:surgery; D017079:Exercise Tolerance; D006801:Humans; D007273:Injections, Intramuscular; D007383:Intermittent Claudication / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D007511:Ischemia / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D007871:Leg Ulcer / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000601:surgery*; D023821:Limb Salvage; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D010865:Pilot Projects; D020127:Recovery of Function; D012039:Regional Blood Flow; D012086:Reoperation; D056910:Republic of Korea; D013997:Time Factors; D016896:Treatment Outcome; D016138:Walking; D014945:Wound Healing; D055815:Young Adult