title: Therapeutic vascular angiogenesis for intractable macroangiopathy-related digital ulcer in patients with systemic sclerosis: a pilot study.
abstract: OBJECTIVE
  SSc causes intractable ischaemic ulcers. To avoid major amputation, we examined the safety and efficacy of therapeutic vascular angiogenesis for digital ulcers due to SSc.
  
  
  METHODS
  A single-centre, open-label pilot study was conducted in patients with an ischaemic digital ulcer [n = 40, mean age 65 years (s.d. 8), Rutherford class III-5 or III-6) due to lcSSc (n = 11) or arteriosclerosis obliterans (ASO; n = 29). Bone marrow mononuclear cells (0.4-5.1 × 10(10) cells in total) were administered into the ischaemic limbs. We evaluated short-term safety and efficacy by means of a pain scale, (99m)Tc-tetrofosmin scintigraphy and transcutaneous oxygen tension (TcPO2) before and 4 weeks after treatment. Also, the 2-year outcome was compared.
  
  
  RESULTS
  There was a case of amputation in each group within 4 weeks after therapy. The pain scale significantly decreased in both groups [lcSSc 93 mm (s.d. 9) to 11 (s.d. 16), P < 0.01; ASO 77 mm (s.d. 22) to 16 (s.d. 13), P < 0.01] and TcPO2 significantly improved [lcSSc 9.0 mmHg (s.d. 9) to 35 (s.d. 14), P < 0.01; ASO 18 mmHg (s.d. 10) to 29 (s.d. 21), P < 0.05). At the 2-year follow-up, the limb amputation rate was 9.1% in lcSSc and 20.7% in ASO (P = 0.36), while the recurrence rate was 18.2% in lcSSc and 17.2% in ASO (P = 0.95). All-cause mortality was 27.3% in lcSSc and 17.2% in ASO (P = 0.65).
  
  
  CONCLUSIONS
  In patients with lcSSc, bone marrow mononuclear cell implantation provides clinical benefit and is safe, without major adverse reactions, and may become an effective strategy.
  
  
  BACKGROUND
  UMIN-CTR, http://www.umin.ac.jp/ctr/index-j.htm, no. UMIN000004112.
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular and Regenerative Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan. gen52@nms.ac.jp.
authors.forename: Gen
authors.initials: G
authors.lastname: Takagi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyamoto
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tara
authors.forename: Sonoko
authors.initials: S
authors.lastname: Kirinoki-Ichikawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kubota
authors.forename: Tomohito
authors.initials: T
authors.lastname: Hada
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Takagi
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Mizuno
mesh_terms: D000368:Aged; D001162:Arteriosclerosis Obliterans / Q000150:complications / Q000601:surgery; D016026:Bone Marrow Transplantation; D023381:Endpoint Determination; D005260:Female; D005385:Fingers / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000502:physiology*; D010147:Pain Measurement; D061214:Patient Safety; D058729:Peripheral Arterial Disease / Q000209:etiology / Q000601:surgery; D010865:Pilot Projects; D012595:Scleroderma, Systemic / Q000150:complications*; D016896:Treatment Outcome; D014456:Ulcer / Q000209:etiology* / Q000601:surgery*; D014652:Vascular Diseases / Q000150:complications* / Q000601:surgery*
keywords: cell transplantation; haematopoietic; scleroderma and related disorders; stem cell; vasculitis