PMID- 22472173
OWN - NLM
STAT- MEDLINE
DCOM- 20131206
LR  - 20130129
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Linking)
VI  - 21
IP  - 9
DP  - 2012
TI  - No difference in intra-arterial and intramuscular delivery of autologous bone 
      marrow cells in patients with advanced critical limb ischemia.
PG  - 1909-18
LID - 10.3727/096368912X636948 [doi]
AB  - 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 +/- 15x10(6) vs. 17 +/- 12x10(6), p < 0.05) 
      despite a similar number of total nucleated cells (4.3 +/- 1.4x10(9) vs. 4.1 +/- 
      1.2x10(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 +/- 2.1x10(9)/L vs. 12.3 +/- 
      4.5x10(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.
FAU - Klepanec, Andrej
AU  - Klepanec A
AD  - Slovak Medical University, Bratislava, Slovakia.
FAU - Mistrik, Martin
AU  - Mistrik M
FAU - Altaner, Cestmir
AU  - Altaner C
FAU - Valachovicova, Martina
AU  - Valachovicova M
FAU - Olejarova, Ingrid
AU  - Olejarova I
FAU - Slysko, Roman
AU  - Slysko R
FAU - Balazs, Tibor
AU  - Balazs T
FAU - Urlandova, Terezia
AU  - Urlandova T
FAU - Hladikova, Daniela
AU  - Hladikova D
FAU - Liska, Branislav
AU  - Liska B
FAU - Tomka, Jan
AU  - Tomka J
FAU - Vulev, Ivan
AU  - Vulev I
FAU - Madaric, Juraj
AU  - Madaric J
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120402
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
SB  - IM
MH  - Aged
MH  - Bone Marrow Transplantation/*methods
MH  - Extremities/*blood supply/surgery
MH  - Female
MH  - Humans
MH  - Injections, Intra-Arterial
MH  - Injections, Intramuscular
MH  - Ischemia/*surgery
MH  - Limb Salvage
MH  - Male
MH  - Skin/*blood supply
EDAT- 2012/04/05 06:00
MHDA- 2013/12/16 06:00
CRDT- 2012/04/05 06:00
PHST- 2012/04/05 06:00 [entrez]
PHST- 2012/04/05 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - ct0531klepanec [pii]
AID - 10.3727/096368912X636948 [doi]
PST - ppublish
SO  - Cell Transplant. 2012;21(9):1909-18. doi: 10.3727/096368912X636948. Epub 2012 Apr 
      2.