title: Long-term clinical outcome after intramuscular transplantation of granulocyte colony stimulating factor-mobilized CD34 positive cells in patients with critical limb ischemia.
abstract: BACKGROUND
  Our phase I/IIa clinical trial revealed that intramuscular transplantation of autologous, GCSF-mobilized CD34+ cells was safe, feasible and potentially effective at week 4 and 12 post cellular therapy in 17 patients with chronic critical limb ischemia (CLI) (5 patients with atherosclerotic peripheral arterial disease (PAD) and 12 with Buerger's disease). However, long-term outcome of the cell therapy has yet to be reported.
  
  
  RESULTS
  Incidence of major clinical events and physiological parameters of limb ischemia were evaluated at week 52, 104, 156 and 208 post CD34+ cell therapy. No patients died by week 104, whereas 3 patients with PAD died by week 156 and 1 patient with Buerger's disease died by week 208 due to cardiac complications. No patients underwent major amputation, whereas 1 patient with Buerger's disease underwent unplanned minor amputation by week 104. CLI-free ratio was 88.2% at week 52 and 104, 92.3% at week 156 and 84.6% at week 208 in all patients. Significant improvement of toe brachial pressure index versus baseline was sustained up to week 208 and that of transcutaneous partial oxygen pressure was kept up to week 156. The Wong-Baker FACES pain rating scale, ulcer size and exercise tolerance significantly improved at week 52, the final evaluation time point, compared with baseline. Subgroup analysis revealed the similar outcome in patients with Buerger's disease.
  
  
  CONCLUSIONS
  Favorable clinical outcomes as well as physiological evidences strongly indicate the long-term benefit of GCSF-mobilized CD34+ cell transplantation for retrieval from CLI, especially in patients with Buerger's disease.
authors.affiliation: Division of Vascular Regeneration Therapy, Unit of Regenerative Medicine, Institute of Biomedical Research and Innovation, Kobe, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujita
authors.forename: Minako
authors.initials: M
authors.lastname: Katayama
authors.forename: Rie
authors.initials: R
authors.lastname: Baba
authors.forename: Maki
authors.initials: M
authors.lastname: Shibakawa
authors.forename: Kimiko
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katakami
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Tomio
authors.initials: T
authors.lastname: Tsukie
authors.forename: Tohru
authors.initials: T
authors.lastname: Nagano
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kurimoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamasaki
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Handa
authors.forename: Yukikatsu
authors.initials: Y
authors.lastname: Okada
authors.forename: Kaori
authors.initials: K
authors.lastname: Kuronaka
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nagata
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Masanori
authors.initials: M
authors.lastname: Fukushima
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asahara
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Kawamoto
mesh_terms: D000328:Adult; D000368:Aged; D000671:Amputation, Surgical; D018952:Antigens, CD34 / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D002908:Chronic Disease; D016638:Critical Illness; D018572:Disease-Free Survival; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007273:Injections, Intramuscular; D007511:Ischemia / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D007564:Japan; D023821:Limb Salvage; D016014:Linear Models; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D020127:Recovery of Function; D012086:Reoperation; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D016019:Survival Analysis; D013919:Thromboangiitis Obliterans / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D016179:Granulocyte Colony-Stimulating Factor