纯化自体外周血CD34+细胞移植治疗下肢重度缺血

目的 探讨纯化自体外周血CD34+细胞移植治疗下肢重度缺血的安全性、可行性和有效性.方法 2009年5月至2010年3月采用纯化自体外周血CD34+细胞移植治疗下肢重度缺血7例,其中血栓闭塞性脉管炎6例,结节性红斑伴血栓形成1例,年龄23～54岁,平均(39±11)岁;均不具备血管重建条件.经G-CSF动员后第5天采集外周血单个核细胞,分选获得纯化CD34+细胞,下肢肌肉局部注射,观察不良反应和缺血缓解情况.结果 7例患者均获技术和保肢成功,移植细胞数(7.1±2.3)×105/kg[(4.6×105～1×106)/kg].7例患者均获随访,随访时间6～14个月,平均(8±3)个月.术后1个月静息痛均明显缓解,Wong-Baker FACES疼痛评分由术前平均7.1±2.0(4～10)降至1.1±1.1(0～2),P=0.0000.无痛步行时间术前平均(4±4)min(1～10 min),术后3个月延长至(12±7)min(5～21 min),P=0.04,术后6个月(20±12)min(6～40 min),P=0.02.术前踝肱指数0.54±0.18(0.41～0.87),术后3个月提高至0.66±0.13(0.52～0.86),P=0.17,术后6个月0.72±0.13(0.56～0.91),P=0.07.6例溃疡中,3例直径＜2 cm者完全愈合,另3例直径＞2 cm者明显缩小.经皮氧分压术前(29±14)mmHg(10～52 mm Hg),术后3个月(46±14)mm Hg(27～63 mm Hg),P=0.04,术后6个月(57±10)mm Hg(41～66 mm Hg),P=0.001.无严重不良反应.结论 初步结果显示纯化自体外周血CD34+细胞移植治疗下肢重度缺血安全,可行,有效.

Abstract：

Objective To evaluate the safety, feasibility and efficacy of transplantation of purified peripheral blood CD34+ cells in treatment of critical ischemia of the lower extremities. Methods From May 2009 to March 2010, seven cases of critical ischemia of the lower extremities received purified peripheral blood CD34+ cells transplantation, among those 6 were caused by thromboangiitis obliterans and 1 by thrombosis coexistent with nodular erythema. Mean age was ( 39 ± 11 ) years ( range 23 - 54 ), and all patients were not suitable for surgical or endovascular revascularization. G-CSF was subcutaneously injected for 5 days before apheresis for peripheral blood mononuclear cells. Then CliniMACS system was used to isolate the CD34+ cells. If the number of CD34+ cells was between 105/kg and 106/kg , they were all intramuscular injected into patients' calf and foot. Results Technical success and limb salvage were achieved in all cases. The mean number of transplanted cells was (7. 1 ±2.3) × 105/kg [ range(4.6 ×105 -1 × 106 )/kg]. All cases were followed-up, ranging from 6 - 14 months (mean 8 ± 3 months). One month after transplantation, the rest pain was obviously relieved in all cases, and the Wong-Baker FACES pain rating scale score significantly decreased from 7. 1 ±2. 0(4 - 10)to 1. 1 ± 1.1 (0 -2) ,P =0. 0000. The pain-free walking distance was significantly improved from (4 ± 4) min (range 1 -10 min)to (12 ± 7 ) min (range 5 - 21min , P =0.04) at 3 months and(20.4 ± 12.5) min(range 6 -40 min, P = 0.02) at 6 months, respectively. The ankle-brachial index increased from 0. 54 ± 0. 18 ( range 0. 41 - 0. 87 ) to 0.66 ±0. 13(range 0. 52-0. 86 , P=0. 17)at 3 months and 0.72 ±0. 13(range 0.56 -0.91, P=0. 07)at 6 months, respectively. Of 6 cases with the toe ulcer, the ulcer was healed in 3 and apparently shrank in 3. Transcutaneous partial oxygen pressure rose from (29 ± 14) mm Hg(range 10 -52 mm Hg)to 46 ±14 mm Hg ( range 27 - 63 mm Hg, P = 0. 04) at 3 months and (57 ± 10) mm Hg( range 41 - 66 mm Hg, P =0.001) at 6 months, respectively. No serious complications were found either perioperatively or postoperatively. Conclusions Transplantation of purified peripheral blood CD34+ cells is safe, feasible and effective in the treatment of critical ischemia of the lower extremities.

Transplantation of purified CD34 + cells from peripheral blood in the treatment of critical ischemia of the lower extremities

Objective To evaluate the safety, feasibility and efficacy of transplantation of purified peripheral blood CD34+ cells in treatment of critical ischemia of the lower extremities. Methods From May 2009 to March 2010, seven cases of critical ischemia of the lower extremities received purified peripheral blood CD34+ cells transplantation, among those 6 were caused by thromboangiitis obliterans and 1 by thrombosis coexistent with nodular erythema. Mean age was ( 39 ± 11 ) years ( range 23 - 54 ), and all patients were not suitable for surgical or endovascular revascularization. G-CSF was subcutaneously injected for 5 days before apheresis for peripheral blood mononuclear cells. Then CliniMACS system was used to isolate the CD34+ cells. If the number of CD34+ cells was between 105/kg and 106/kg , they were all intramuscular injected into patients' calf and foot. Results Technical success and limb salvage were achieved in all cases. The mean number of transplanted cells was (7. 1 ±2.3) × 105/kg [ range(4.6 ×105 -1 × 106 )/kg]. All cases were followed-up, ranging from 6 - 14 months (mean 8 ± 3 months). One month after transplantation, the rest pain was obviously relieved in all cases, and the Wong-Baker FACES pain rating scale score significantly decreased from 7. 1 ±2. 0(4 - 10)to 1. 1 ± 1.1 (0 -2) ,P =0. 0000. The pain-free walking distance was significantly improved from (4 ± 4) min (range 1 -10 min)to (12 ± 7 ) min (range 5 - 21min , P =0.04) at 3 months and(20.4 ± 12.5) min(range 6 -40 min, P = 0.02) at 6 months, respectively. The ankle-brachial index increased from 0. 54 ± 0. 18 ( range 0. 41 - 0. 87 ) to 0.66 ±0. 13(range 0. 52-0. 86 , P=0. 17)at 3 months and 0.72 ±0. 13(range 0.56 -0.91, P=0. 07)at 6 months, respectively. Of 6 cases with the toe ulcer, the ulcer was healed in 3 and apparently shrank in 3. Transcutaneous partial oxygen pressure rose from (29 ± 14) mm Hg(range 10 -52 mm Hg)to 46 ±14 mm Hg ( range 27 - 63 mm Hg, P = 0. 04) at 3 months and (57 ± 10) mm Hg( range 41 - 66 mm Hg, P =0.001) at 6 months, respectively. No serious complications were found either perioperatively or postoperatively. Conclusions Transplantation of purified peripheral blood CD34+ cells is safe, feasible and effective in the treatment of critical ischemia of the lower extremities.