title: Clinical study of therapeutic angiogenesis by autologous peripheral blood stem cell (PBSC) transplantation in 92 patients with critically ischemic limbs.
abstract: Patients with critically ischemic limbs due to maintenance hemodialysis and diabetes are increasing in number markedly in Japan. The difficulty of treating critically ischemic limbs is well recognized. Despite active medication and surgical therapy, many critically ischemic limbs are amputated. Ninety-two patients with critically ischemic limbs were treated by transplantation of autologous peripheral blood stem cells (PBSCs). The stem cells were mobilized into the peripheral blood by administration of granulocyte colony stimulating factor (G-CSF). The mobilized mononuclear cells were separated by an apheresis technique using a centrifuge. The separated mononuclear cells contained approximately 4.0 x 10(7) CD34-positive cells. The collected cell suspension was divided into aliquots of 0.5-1.0 ml and transplanted into the muscle of ischemic limbs at 50-70 transplantation points. At 1.5 months after PBSC transplantation, a strong immunostaining of CD34-positive cells and factor VIII, as well as capillary formation, was observed in the muscles into which stems cells had been transplanted. In each patient tested, the serum vascular endothelial growth factor (VEGF) level increased after stem cell transplantation; the mean VEGF level increased by 176%. Of 11 diabetic patients (DM) who were not receiving hemodialysis (HD), there were no amputees regardless of their Fontaine classification. Of 19 patients in the HD(+)DM(-) category, there were no amputations in Fontaine stage I, II, and III patients, whereas three limbs and one toe were amputated in Fontaine stage IV patients. Of 13 patients in the HD(-)DM(+) category, none of the Fontaine stage I, II, or III patients underwent amputation, but six Fontaine stage IV patients underwent amputation. Of 49 patients in the HD(+)DM(+) category, 38 (78%) were classified as Fontaine stage IV, 71% (27/38) of whom had a toe or a limb amputated. In nine patients over 80 years of age, one toe and one limb were amputated. Nondiabetic, nondialyzed patients with ischemic limbs are strongly indicated for stem cell transplantation regardless of Fontaine classification. Therapeutic angiogenesis is effective for critically ischemic limbs resulting from hemodialysis and diabetes until Fontaine stage III, but is of limited effectiveness for stage IV cases.
authors.affiliation: Surgical Department, Sapporo Hokuyu Hospital, 6-6 Higashisapporo, Sapporo 003-0006, Japan. tosho@hokuyu-aoth.org
authors.forename: Akio
authors.initials: A
authors.lastname: Kawamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Horie
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tsuda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Abe
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamada
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Egawa
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Iida
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakata
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Onodera
authors.forename: Tohru
authors.initials: T
authors.lastname: Tamaki
authors.forename: Hidenori
authors.initials: H
authors.lastname: Furui
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Kukita
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Meguro
authors.forename: Motoki
authors.initials: M
authors.lastname: Yonekawa
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003925:Diabetic Angiopathies / Q000601:surgery; D003928:Diabetic Nephropathies / Q000628:therapy; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007511:Ischemia / Q000503:physiopathology / Q000601:surgery*; D007866:Leg / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D036102:Peripheral Blood Stem Cell Transplantation; D010991:Plethysmography; D006435:Renal Dialysis; D013817:Thermography; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D042461:Vascular Endothelial Growth Factor A