Autologous transplantation of bone marrow mononuclear cells improved ischemic peripheral neuropathy in humans
Autologous transplantation of bone marrow mononuclear cells improved ischemic peripheral neuropathy in humans
复制标题
自体骨髓单核细胞移植可改善人类缺血性周围神经病
DOI：
10.1016/j.jacc.2010.02.050
复制
发表时间：
2010
影响因子：
24
通讯作者：
Imaizumi T(他8人11番目)
中科院分区：
文献类型：
--
作者：
Arima K;Kai H;Imaizumi T(他8人11番目)
致编辑：缺血性周围神经病是一个术语，用于描述外周动脉阻塞性疾病患者周围神经的神经功能缺损 (1)。尽管缺血性周围神经病变是严重肢体缺血导致生活质量受损的主要并发症，但目前尚无针对缺血性神经病变的有效治疗方法。最近，有报道称，使用血管内皮生长因子 (VEGF) 基因转移治疗严重肢体缺血的血管生成可改善动物 (2) 和人类 (3) 的缺血性神经病变。我们报道了使用骨髓单核细胞 (BM-MNC) 自体移植治疗外周动脉疾病的治疗性血管生成增加了肢体灌注并改善了临床状况，例如缺血性疼痛、跛行和缺血性溃疡 (4, 5)。因此，我们研究了 BM-MNC 的自体移植是否会改善人类严重肢体缺血的缺血性神经病。 We enrolled 14 patients with angiographically-proven critical limb ischemia (Table 1).每例患者在1条缺血腿（治疗肢体）中进行自体BM-MNCs（4.89 5.21 109个细胞）移植，并在另一条腿（对照肢体）中注射生理盐水。移植前和移植后1个月，我们检查了主观症状（视觉模拟量表作为静息痛严重程度、无痛步行距离的指标）、踝肱压力指数和数字减影血管造影评分。记录胫骨运动神经传导速度（MNCV）、腓肠感觉神经传导速度（SNCV）、复合肌肉动作电位（CMAP）、胫骨和腓肠感觉神经动作电位（SNAP）以及定量振动阈值时间（QVT）。我们还测量了 23 名年龄和性别相似的健康受试者的 MNCV、SNCV、CMAP 和 SNAP。这项研究对评估神经功能的研究者不知情。该方案得到了久留米大学机构伦理委员会的批准。所有受试者均获得书面知情同意书。治疗仅显着改善了治疗肢体的主观症状和外周血灌注（表 1）。可以测量所有患者的治疗肢体和 12 名患者的对照肢体的 MNCV 和 CMAP。治疗前，治疗肢体的 MNCV 和 CMAP 均显着小于健康组（表 1）。治疗仅在治疗肢体中显着增加 MNCV 和 CMAP。治疗使 MNCV 和 CMAP 恢复至健康组的水平。治疗后，仅治疗肢体的 QVT 显着改善，而对照肢体则没有显着改善（表 1）。患者的SNCV和SNAP与健康组没有差异，治疗对其没有影响（表1）。本研究的主要结果如下。首先，自体 BM-MNC 移植改善了严重肢体缺血患者的主观缺血和神经病理症状。其次，治疗不仅改善了周围血液灌注，还改善了周围神经功能。这项研究证实了我们之前的研究结果 (4, 5)，即自体 BM-MNC 移植改善了治疗肢体的踝臂压力指数、数字减影血管造影评分和主观症状。此外，BM-MNC 移植改善了治疗肢体的客观周围神经功能（MNCV、CMAP 和 QVT），但没有改善对照肢体，表明这些效果与自然病程或非特异性效果无关。因此，自体 BM-MNC 移植不仅可以改善外周血灌注，还可以改善缺血性周围神经病变……
To the Editor: Ischemic peripheral neuropathy is a term used to describe the neurological deficits of peripheral nerves in patients with peripheral artery obstructive disease (1). Although ischemic peripheral neuropathy is a major complication of critical limb ischemia resulting in impaired quality of life, effective treatment for ischemic neuropathy is not available at present. Recently, it has been reported that therapeutic angiogenesis using vascular endothelial growth factor (VEGF) gene transfer for critical limb ischemia improves ischemic neuropathy in animals (2) and humans (3). We reported that therapeutic angiogenesis using autologous transplantation of bone marrow mononuclear cells (BM-MNCs) for peripheral artery disease increased limb perfusion and improved clinical conditions, such as ischemic pain, claudication, and ischemic ulcer (4, 5). Therefore, we examined whether autologous transplantation of BM-MNCs would improve ischemic neuropathy with critical limb ischemia in humans. We enrolled 14 patients with angiographically-proven critical limb ischemia (Table 1). In each patient, autologous transplantation of BM-MNCs (4.89 5.21 109 cells) was performed in 1 ischemic leg (treated limb), and saline was injected into another leg (control limb). Before and 1 month after transplantation, we examined subjective symptoms (visual analogue scale as an index of rest pain severity, pain-free walking distance), ankle brachial pressure index, and digital subtraction angiography score. Tibial motor nerve conduction velocity (MNCV), sural sensory nerve conduction velocity (SNCV), compound muscle action potential (CMAP), tibial and sural sensory nerve action potential (SNAP), and quantitative vibration threshold time (QVT) were recorded. We also measured MNCV, SNCV, CMAP, and SNAP of 23 ageand sex-similar healthy subjects. This study was blinded to the investigator who assessed nerve functions. The protocol was approved by the institutional ethics committee of Kurume University. Written informed consent was obtained from all subjects. Treatment significantly improved subjective symptoms and peripheral blood perfusion only in the treated limb (Table 1). The MNCV and CMAP could be measured in the treated limb of all patients, and in the control limb of 12 patients. Before treatment, both MNCV and CMAP were significantly smaller in the treated limb than in the healthy group (Table 1). Treatment significantly increased both MNCV and CMAP only in the treated limb. Treatment recovered MNCV and CMAP to the level of the healthy group. The QVT was significantly improved only in the treated limb, but not in the control limb after treatment (Table 1). The SNCV and SNAP of the patients did not differ from those of the healthy group, and the treatment did not affect them (Table 1). The major findings of this study are as follows. First, autologous BM-MNC transplantation improved subjective ischemic and neuropathic symptoms in patients with critical limb ischemia. Second, the treatment improved not only peripheral blood perfusion but also peripheral nerve function. This study confirmed our previous findings (4, 5) that autologous BM-MNC transplantation improved ankle brachial pressure index, digital subtraction angiography score, and subjective symptoms in treated limbs. Furthermore, BM-MNC transplantation improved objective peripheral nerve functions (MNCV, CMAP, and QVT) in the treated limb but not in the control limb, suggesting that the effects were not related to natural course or nonspecific effects. Thus, autologous BM-MNC transplantation might improve not only peripheral blood perfusion but also ischemic peripheral neuropathy …
严重肢体缺血患者肌内 phVEGF165 基因转移后慢性缺血性神经病变的改善。
影响因子：
--
作者：
D. Simovic;J. Isner;A. Ropper;A. Pieczek;D. H. Weinberg
通讯作者：
D. H. Weinberg