人脐血间质干细胞静脉输注治疗酒精性股骨头坏死

Human umbilical cord blood-derived mesenchymal stem cells via intravenous infusion for the treatment of alcoholic osteonecrosis of the femoral head

目的:评价静脉输注人脐血间质干细胞治疗酒精性股骨头坏死患者的有效性及安全性。方法:①实验对象:选取2005-11/2006-09在郑州市第二人民医院外一科住院和门诊收治的双侧酒精性缺血性股骨头坏死患者13例(共26髋),Ⅱ期6例12髋,Ⅲ期4例8髋,Ⅳ期3例6髋,平均年龄38.5岁,均有酗酒史,4例合并激素应用史。实验经医院医学伦理委员会批准,13例患者对治疗方案均知情同意。新生儿脐血由河南省红十字血液中心提供,产妇及其家属均签署知情同意书。②实验方法:以无菌塑料采血袋密闭式采集足月新生儿脐带血80～140mL,22℃下1500r/min离心30min。通过手背浅静脉将分离获得的人脐血间质干细胞输注入股骨头坏死患者体内,细胞数≥1×108/份,2份/次,间隔4d后再次输注,共3次,此为1个疗程。共3个疗程,每个疗程间隔2～3个月。每个疗程结束后嘱其进行功能锻炼,以游泳为主。③实验评估:细胞移植结束后2,4,6个月,观察患者髋关节疼痛程度、疼痛性质及疼痛时间变化、髋关节外展与内旋功能变化、行走距离及步态变化;细胞移植后6个月,观察X线图像变化、股骨头形态学变化;观察细胞移植过程中及移植后的不良反应。结果:13例患者均完成细胞移植后6个月随访。①患者临床症状改善:13例患者髋关节疼痛均有不同程度的缓解或消失,有效率100%;髋关节外展与内旋功能改善12例(92%);行走距离及步态变化改善12例(92%),生活质量明显提高。②细胞移植后6个月X线变化:13例患者中,8例可见不同程度的股骨头坏死区骨质密度的改变,坏死区有吸收、缩小,股骨头形态变圆滑规整,4例股骨头形态恢复正常,另外1例无变化。未出现股骨头坏死较术前加重的患者。③细胞移植后6个月股骨头形态学变化:13例患者中,7髋(7/26,26.92%)股骨头恢复正常,15髋(15/26,57.69%)股骨头坏死区缩小,4髋(4/26,15.38%)无变化。④不良事件和副反应:在细胞移植过程中及移植后均未发生并发症和不良反应。结论:经手背浅静脉多份、多次输注脐血间质干细胞,方法简便且安全有效,是全身整体治疗酒精性股骨头坏死的一种新手段。

AIM： To assess the efficacy and salty of human umbilical cord blood-derived mesenchymal stem cells （HUCB-MSCs） by intravenous infusion on the treatment of alcoholic osteonecrosis of the femoral head （AOFH）. METHODS：①Totally 13 patients with bilateral AOFH （26 hips） and with an average age of 38.5 years were enrolled from Hospitalization Department and Out-Patient Clinic of First Department of General Surgery, Zhengzhou ,Second People＇s Hospital from November 2005 to September 2006. There were 6 cases （12 hips） at phase Ⅱ, 4 cases （8 hips） at stage Ⅲand 3 cases （6 hips） at stage Ⅳ. All patients had a history of alcohol abuse and 4 cases of them were combined with a history of hormone utilization. The experiment was approached by Hospital Ethics Committee. All 13 patients knew the therapeutic regimen and agreed to participate in the trial. Neonatal cord blood was collected from Henan Red-cross Blood Center. The puerperants and their family members signed the informed consent. ②80-140 mL full-term infant cord blood was collected with sterile plastic closed tightly and centrifuged at 1 500 r/min at 22℃ for 30 minutes. HUCB-MSCs were transplanted in superficial vein in the back of hand of AOFH patients at least 1 ×10^8 in a share, once two shares, with an interval of 4 days for 3 times as a course of treatment, totally 3 courses with an interval of 2-3 months in each course. Functional exercise mainly swimming was instructively performed after each course. Pain degree, pain property and pain time of hip joint, abducens and adtorsion of hip joint, walking distance and walking were observed at months 2, 4 and 6 after transplantation. Six months after transplantation, X-ray image and femoral morphology were observed and adverse reaction in transplantation and after transplantation was also observed. RESULTS： Totally 13 patients were followed up for 6 months after transplantation.①Improvement of clinical symptom： Pain of hip joint relieved to some extent or disappeared in 13 cases with the effective rate of 100%. Abducens and adtorsion of hip joint were improved in 12 cases （92%）. Walking distance and walking were ameliorated in 12 cases （92%）. Quality of life was markedly elevated in these patients. ②X-ray change 6 months after transplantation： Of the 13 cases, bone density was changed to some extent, resorption or diminution appeared, and femoral head became tactful and regular at osteonecrosis region in 8 cases. Femoral head recovered to normal in 4 cases and no change was found in another case. None of them became severe compared with before transplantation. ③Femoral morphology 6 months after transplantation： Of the 13 cases, femoral head recovered to normal in 7 hips （7/26,26.92%）; Necrotic zone became small in 15 hips （15/26,57.69%）, and no change was seen in 4 hips （4/26,15.38%）. ④Side event and adverse reaction： No complication or adverse reaction occurred in transplantation and after transplantation. CONCLUSION： Multiple HUCB-MSCs transplantation in superficial vein in the back of hand, which is convenient, safe and effective, is a new approach for AOFH.