Durdu Serkan, Akar Ahmet Ruchan, Arat Mutlu, Sancak Tanzer, Eren Neyyir Tuncay, Ozyurda Umit
Department of Cardiovascular Surgery, Heart Center, Ankara University School of Medicine, Ankara, Turkey.
J Vasc Surg. 2006 Oct;44(4):732-9. doi: 10.1016/j.jvs.2006.06.023. Epub 2006 Aug 22.
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).
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 >or=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.
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%).
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.
本研究调查了自体骨髓单个核细胞（ABMMNC）植入治疗血栓闭塞性脉管炎（伯格氏病）所致严重肢体缺血（CLI）患者的疗效和安全性。
本研究纳入了28例患者（25例男性和3例女性），中位年龄44岁（范围25 - 54岁），患有血栓闭塞性脉管炎且单侧严重肢体缺血，定义为肢体出现缺血性静息痛，伴或不伴有不愈合溃疡。患者接受多次将去除红细胞并减少体积的ABMMNC注射到腓肠肌、跖间区域和足背（n = 26）或前臂（n = 2），而在缺血程度较轻的对侧肢体注射生理盐水。这些患者对先前的伊洛前列素输注无反应且戒烟≥6个月，并且不适合进行非手术或手术血管重建。主要终点是最重要病变完全愈合，同时避免大截肢或小截肢，从基线到6个月随访期间无需使用镇痛药即可缓解静息痛，以及治疗的安全性和可行性。次要终点是踝肱压力指数和峰值步行时间的变化、侧支血管形成或重塑的血管造影证据以及生活质量评估。两名对治疗分配不知情的研究人员进行图像分析。
单侧肌肉内注射ABMMNC未出现任何并发症。平均随访时间为16.6±7.8个月（范围7.6至33.8个月）。随访期间仅有1例患者需要进行趾截肢。与基线值相比，8例患者在3个月时踝肱压力指数变化>0.15，14例患者在6个月时变化>0.15。在6个月时，患者的静息痛评分（P <.0001）、峰值步行时间（P <.0001）和生活质量（P <.0083）均有显著改善。15例（83%）患有缺血性溃疡的患者最重要病变完全愈合，所有患者无需使用麻醉性镇痛药即可缓解静息痛。ABMMNC植入前和植入后6个月的数字减影血管造影研究显示，22例患者（78.5%）在受影响动脉周围形成了血管侧支网络。
对于血栓闭塞性脉管炎和对其他治疗方式难治的严重肢体缺血患者，ABMMNC植入可能是实现治疗性血管生成的一种安全替代方法。
