Transplantation of purified CD34+ cells in the treatment of critical limb ischemia
Transplantation of purified CD34+ cells in the treatment of critical limb ischemia
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DOI：
10.1016/j.jvs.2013.01.037
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发表时间：
2013-08-01
影响因子：
4.3
通讯作者：
Mendelsohn, Farrell Owen
中科院分区：
文献类型：
--
作者：
Dong, Zhihui;Chen, Bin;Mendelsohn, Farrell Owen
背景资料：本研究探讨了肌内注射从粒细胞集落刺激因子（G-CSF）动员的外周血单个核细胞（PB-MNCs）中分离的CD 34+细胞治疗严重肢体缺血（CLI）患者的可行性、安全性和有效性，这些患者被认为不太可能通过开放旁路或血管内方法成功进行长期血运重建。细胞疗法代表了该CLI患者亚组的一种新治疗方式。迄今为止，骨髓或PB-MNC通常用于移植。目前的试点研究调查是否只有纯化的CD 34+细胞移植将能够胜任缺血缓解和肢体salvage.Methods：从2009年5月至2011年7月，25例患者（平均年龄，44 +/- 12岁），25个下肢和3个上肢进行了治疗。以5至10 μ g/kg的剂量皮下给予G-CSF 5天后，进行单采血液成分术和免疫磁性分离以获得分离的CD 34+细胞，然后将其肌内注射到缺血部位。患者分为三组：低剂量，10（5）/kg;中剂量，5 x 10（5）/kg;高剂量，10（6）/kg。结果：随访6 ~ 33个月，Wong-Baker FACES疼痛评分（WFPRSS）从7 ± 2分下降到3 ± 3分（P < .001）和1 +/- 2（P < .001）;在3个月和6个月时，峰值无痛步行时间分别从4 +/- 3增加到13 +/- 7（P < .001）和18 +/- 6分钟（P < .001），踝臂指数从0.46 +/- 0.21增加到0.60 +/- 0.17经皮氧分压从27 +/- 10增加到41 +/- 11（P <.001）和55 +/- 12 mm Hg（P <.001）。14名患者中有10名溃疡愈合; 4名患者需要膝上或膝下截肢
Background: This study investigated the feasibility, safety, and efficacy of the intramuscular injection of CD34+ cells isolated from peripheral blood mononuclear cells (PB-MNCs) mobilized by granulocyte colony-stimulating factor (G-CSF) for the management of patients with critical limb ischemia (CLI) who were considered unlikely to have successful long-term revascularization with open bypass or endovascular methods. Cell therapy represents a new treatment modality for this subgroup of patients with CLI. To date, bone marrow or PB-MNCs have usually been used for transplantation. The current pilot study investigated whether the transplantation of purified CD34+ cells only would be competent in ischemia relief and limb salvage.Methods: From May 2009 to July 2011, 25 patients (mean age, 44 +/- 12 years) were enrolled, and 25 lower extremities and three upper extremities were treated. After subcutaneous administration of G-CSF for 5 days at a dose of 5 to 10 mu g/kg, apheresis and immunomagnetic separation were performed to acquire the isolated CD34+ cells, which were then intramuscularly injected into the ischemic sites. The patients were divided into three groups: low-dose, 10(5)/kg; medium-dose, 5 x 10(5)/kg; and high-dose, 10(6)/kg. The overall outcomes among all patients and the comparison among the groups were evaluated.Results: During the follow-up of 6 to 33 months, the overall outcomes showed that the Wong-Baker FACES pain rating scale score (WFPRSS) decreased from 7 +/- 2 to 3 +/- 3 (P < .001) and 1 +/- 2 (P < .001) at 1 and 2 months, respectively; at 3 and 6 months, respectively, the peak pain-free walking time increased from 4 +/- 3 to 13 +/- 7 (P < .001) and 18 +/- 6 minutes (P < .001), the ankle-brachial index increased from 0.46 +/- 0.21 to 0.60 +/- 0.17 (P = .003) and 0.67 +/- 0.15 (P = .001), and the transcutaneous partial oxygen pressure increased from 27 +/- 10 to 41 +/- 11 (P < .001) and 55 +/- 12 mm Hg (P < .001). Ulcers were healed in 10 of the 14 patients; four patients required above-knee or below-knee amputation