title: No difference in intra-arterial and intramuscular delivery of autologous bone marrow cells in patients with advanced critical limb ischemia.
abstract: Stem cell therapy has been proposed to be an alternative therapy in patients with critical limb ischemia (CLI), not eligible for endovascular or surgical revascularization. We compared the therapeutic effects of intramuscular (IM) and intra-arterial (IA) delivery of bone marrow cells  (BMCs) and investigated the factors associated with therapeutic benefits. Forty-one patients (mean age, 66 ± 10 years; 35 males) with advanced CLI (Rutherford category, 5 and 6) not eligible for revascularization were randomized to treatment with 40 ml BMCs using local IM (n  = 21) or selective IA infusion (n = 20). Primary endpoints were limb salvage and wound healing. Secondary endpoints were changes in transcutaneous oxygen pressure (tcpO(2)), quality-of-life questionnaire (EQ5D), ankle-brachial index (ABI), and pain scale (0-10). Patients  with limb salvage and wound healing were considered to be responders to BMC therapy. At 6-month follow-up, overall limb salvage was 73% (27/37) and 10 subjects underwent major amputation. Four patients died unrelated to stem cell therapy. There was significant improvement in tcpO(2)  (15 ± 10 to 29 ± 13 mmHg, p < 0.001), pain scale (4.4 ± 2.6 to 0.9 ± 1.4, p < 0.001), and EQ5D (51 ± 15 to 70 ± 13, p < 0.001) and a significant decrease in the Rutherford category of CLI (5.0 ± 0.2 to 4.3 ±  1.6, p < 0.01). There were no differences among functional parameters in patients undergoing IM versus IA delivery. Responders (n = 27) were characterized by higher CD34(+) cell counts in the bone marrow concentrate (CD34(+) 29 ± 15×10(6)  vs. 17 ± 12×10(6), p < 0.05) despite a similar number of total nucleated cells (4.3 ± 1.4×10(9) vs. 4.1 ± 1.2×10(9), p = 0.66) and by a lower level of C-reactive protein (18 ± 28 vs. 100 ±  96 mg/L, p < 0.05) as well as serum leukocytes (8.3 ± 2.1×10(9)/L vs. 12.3 ± 4.5×10(9)/L, p < 0.05) as compared with nonresponders (10 patients). Both IM and IA delivery of autologous stem cells are effective therapeutic strategies  in patients with CLI. A higher concentration of CD34(+) cells and a lower degree of inflammation are associated with better clinical therapeutic responses.
authors.affiliation: Slovak Medical University, Bratislava, Slovakia.
authors.forename: Andrej
authors.initials: A
authors.lastname: Klepanec
authors.forename: Martin
authors.initials: M
authors.lastname: Mistrik
authors.forename: Cestmir
authors.initials: C
authors.lastname: Altaner
authors.forename: Martina
authors.initials: M
authors.lastname: Valachovicova
authors.forename: Ingrid
authors.initials: I
authors.lastname: Olejarova
authors.forename: Roman
authors.initials: R
authors.lastname: Slysko
authors.forename: Tibor
authors.initials: T
authors.lastname: Balazs
authors.forename: Terezia
authors.initials: T
authors.lastname: Urlandova
authors.forename: Daniela
authors.initials: D
authors.lastname: Hladikova
authors.forename: Branislav
authors.initials: B
authors.lastname: Liska
authors.forename: Jan
authors.initials: J
authors.lastname: Tomka
authors.forename: Ivan
authors.initials: I
authors.lastname: Vulev
authors.forename: Juraj
authors.initials: J
authors.lastname: Madaric
mesh_terms: D000368:Aged; D016026:Bone Marrow Transplantation / Q000379:methods*; D005121:Extremities / Q000098:blood supply* / Q000601:surgery; D005260:Female; D006801:Humans; D007269:Injections, Intra-Arterial; D007273:Injections, Intramuscular; D007511:Ischemia / Q000601:surgery*; D023821:Limb Salvage; D008297:Male; D012867:Skin / Q000098:blood supply*