Autologous bone-marrow mononuclear cell implantation for patients with Rutherford grade II-III thromboangiitis obliterans

被引:118
作者
Durdu, Serkan
Akar, Ahmet Ruchan
Arat, Mutlu
Sancak, Tanzer
Eren, Neyyir Tuncay
Ozyurda, Umit
机构
[1] Ankara Univ, Sch Med, Ctr Heart, Dept Cardiovasc Surg, TR-06340 Ankara, Turkey
[2] Ankara Univ, Sch Med, Dept Haematol, TR-06100 Ankara, Turkey
[3] Ankara Univ, Ibn Sina Hosp, Dept Radiol, TR-06100 Ankara, Turkey
关键词
D O I
10.1016/j.jvs.2006.06.023
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background: This study investigated the efficacy and safety of autologous bone marrow-mononuclear cells (ABMMNC) implantation in patients with critical limb ischemia (CLI) due to thromboangiitis obliterans (Buerger's disease). Methods: The study comprised 28 patients (25 men and 3 women) with a median age of 44 years (range, 25-54 years) who had thromboangiitis obliterans and unilateral critical limb ischemia, defined as ischemic rest pain in a limb with or without nonhealing ulcers. The patients received multiple injections of erythrocyte-depleted and volume-reduced ABMMNC into the gastrocnemius muscle, the intermetatarsal region, and the feet dorsum (n = 26) or forearm (n = 2) vs saline injections into the less ischemic contralateral limbs. The patients were nonresponders to previous Iloprost infusion and smoking cessation >= 6 months and were not candidates for nonsurgical or surgical revascularization. Primary end points were the total healing of the most important lesion while avoiding major or minor amputation, the relief of rest pain without the need for analgesics from baseline to 6 months' follow-up, and the safety and feasibility of the treatment. Secondary end points were the changes in ankle-brachial pressure index and peak walking time, the angiographic evidence of collateral vessel formation or remodeling, and the quality-of-life assessment. Two investigators blinded for treatment assignment performed image analyses. Results: Unilateral intramuscular administration of ABMMNC was not associated with any complications. The mean follow-up time was 16.6 +/- 7.8 months (range, 7.6 to 33.8 months). Only one patient required toe amputation during follow-up. A change in the ankle-brachial pressure index > 0.15 was achieved in 8 patients at 3 months and in 14 patients at 6 months compared with baseline values. At 6 months, patients demonstrated a significant improvement in rest pain scores (P < .0001), peak walking time (P < .0001), and quality of life (P < .0083). Total healing of the most important lesion was achieved in 15 patients (83%) with ischemic ulcers, and relief of rest pain without the need of narcotic analgesics improved in all patients. Digital subtraction angiography studies before and 6 months after the ABMMNC implantation showed vascular collateral networks had formed across the affected arteries in 22 patients (78.5%). Conclusions: ABMMNC implantation could be a safe alternative to achieve therapeutic angiogenesis in patients with thromboangiitis obliterans and critical limb ischemia refractory to other treatment modalities.
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页码:732 / 739
页数:8
相关论文
共 34 条
[1]   Regenerative medicine for cardiovascular disorders-new milestones: Adult stem cells [J].
Akar, AR ;
Durdu, S ;
Corapcioglu, T ;
Ozyurda, U .
ARTIFICIAL ORGANS, 2006, 30 (04) :213-232
[2]  
Akar AR, 2005, BONE MARROW TRANSPL, V35, pS76
[3]  
AKAR AR, 2004, TURKISH J HAEMATOL, V21, P13
[4]  
Arslan Ö, 2000, BLOOD, V96, p325B
[5]   Endothelial progenitor cells for postnatal vasculogenesis [J].
Asahara, T ;
Kawamoto, A .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2004, 287 (03) :C572-C579
[6]   Isolation of putative progenitor endothelial cells for angiogenesis [J].
Asahara, T ;
Murohara, T ;
Sullivan, A ;
Silver, M ;
vanderZee, R ;
Li, T ;
Witzenbichler, B ;
Schatteman, G ;
Isner, JM .
SCIENCE, 1997, 275 (5302) :964-967
[7]   Angiogenesis in transmyocardial revascularization: Comparison of laser versus mechanical punctures [J].
Chu, VF ;
Giaid, A ;
Kuang, JQ ;
McGinn, AN ;
Li, CM ;
Pelletier, MP ;
Chiu, RCJ .
ANNALS OF THORACIC SURGERY, 1999, 68 (02) :301-308
[8]   Long-term survival and amputation risk in Thromboangiitis obliterans (Buerger's disease) [J].
Cooper, LT ;
Tse, TS ;
Mikhail, MA ;
McBane, RD ;
Stanson, AW ;
Ballman, KV .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2004, 44 (12) :2410-2411
[9]   Therapeutic interventions for enhancing collateral development by administration of growth factors: basic principles, early results and potential hazards [J].
Epstein, SE ;
Fuchs, S ;
Zhou, YF ;
Baffour, R ;
Kornowski, R .
CARDIOVASCULAR RESEARCH, 2001, 49 (03) :532-542
[10]  
Esato K, 2002, CELL TRANSPLANT, V11, P747