title: Repeated local implantation of autologous peripheral blood mononuclear cells for the treatment of ischaemic digits in patients with connective tissue diseases.
abstract: OBJECTIVE
  Blood flow in fingers and toes is often impaired in patients with CTDs, mandating amputation in some. Our previous study showed that a single implantation of autologous bone marrow cells is as effective as peripheral blood mononuclear cells (MNCs) to restore impaired blood flow, although neither has long-lasting efficacy. In this study, autologous peripheral blood MNCs were implanted repeatedly to evaluate a better efficacy.
  
  
  METHODS
  Three patients with SSc, two with microscopic polyangiitis and one with MCTD were enrolled. All patients had severe RP, ulcers and/or necrosis in the extremities. MNCs were obtained from 400 to 1600 ml of peripheral blood and implanted into 20-80 different sites in the palms and/or soles. This procedure was repeated every 3 months up to 1 year. Humoral factors were measured by ELISAs.
  
  
  RESULTS
  Visual analogue scale scores for pain, coldness and subjective satisfaction were improved after implantation in all patients. Pre-treatment ulcers in five patients were cured after repeated implantations. Angiography showed increased vasculature compared with baseline. Serum levels of VEGF increased after implantation, whereas levels of IL-1β, fibroblast growth factor and endostatin had variable results. None of the patients had any adverse reactions during a follow-up period of up to 3 years.
  
  
  CONCLUSIONS
  Repeated implantation of peripheral blood MNCs was effective and safe for the treatment of recalcitrant ulcers developing in ischaemic digits and toes in patients with CTD.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi-ken 329-0498, Japan. y.kamata@jichi.ac.jp
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kamata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwamoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Muroi
authors.forename: Seiji
authors.initials: S
authors.lastname: Minota
mesh_terms: D000368:Aged; D005346:Fibroblast Growth Factors / Q000097:blood; D005385:Fingers / Q000098:blood supply*; D005500:Follow-Up Studies; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D007511:Ischemia / Q000097:blood / Q000209:etiology* / Q000601:surgery*; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D055953:Microscopic Polyangiitis / Q000150:complications*; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000150:complications*; D010147:Pain Measurement; D017060:Patient Satisfaction; D012039:Regional Blood Flow / Q000502:physiology; D014034:Toes / Q000098:blood supply*; D014182:Transplantation, Autologous / Q000009:adverse effects; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D053583:Interleukin-1beta; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors