脐血单核细胞移植治疗慢性完全性脊髓损伤Ⅱ期临床试验的安全性和疗效评估  

PhaseⅡclinical trial assessing safety and efficacy of umbilical cord blood mononuclear cell transplant therapy of chronic complete spinal cord injury

作　　者：封亚平 Wise Young 朱辉 封雨 邓洵鼎 谢佳芯 张社敏 方芳 石静 陈永和 郑爽 Feng Yaping;Wise Young;Zhu Hui;Feng Yu;Deng Xunding;Xie Jiaxin;Zhang Shemin;Fang Fang;Shi Jing;Chen Yonghe;Zheng Shuang(Department of Neurosurgery,920 Hospital of Joint Logistics Support Force,Kunming 650032,China;W.M.Keck Center for Collaborative Neuroscience,Rutgers University,Piscataway 08855,New Jersey,United States;China Spinal Cord Injury Network,Hong Kong 999077,China)

机构地区：[1]联勤保障部队第九二〇医院神经外科,昆明650032 [2]美国新泽西罗格斯州立大学神经科学中心,美国皮斯卡特维08855 [3]中国脊髓损伤研究协作组,中国香港999077

出　　处：《中华神经创伤外科电子杂志》2020年第4期196-201,共6页Chinese Journal Of Neurotraumatic Surgery：Electronic Edition

基　　金：军队临床高新技术重大项目(2010gxjs042);云南省社会发展科技计划项目(2010CA005)。

摘　　要：目的评估人类白细胞抗原(HLA≥4:6)配型的脐血单核细胞(UCBMC)移植治疗慢性完全性脊髓损伤(SCI)的安全性、可行性、有效性以及最佳细胞剂量和联合使用甲基强的松龙(MP)、碳酸锂对细胞移植的作用。方法选取联勤保障部队第九二〇医院神经外科自2011年2月至2014年1月收治的20例SCI患者,按照随机数字表法分为5组(A、B、C、D、E组),每组4例受试者。在患者损伤上下缘脊神经背根入处的4个点(上下各2点)注射UCBMC,A、B、C组分别为每点各注射4、8和16μL(100000 UCBMC/μL,640万细胞)到SCI部位的上方和下方脊神经背根入处,D组为16μL细胞注射加30 mg/kg MP静脉注射,E组为16μL细胞注射加MP和口服碳酸锂(750 mg/d),一个疗程6周。受试者进行3~6个月的强化步行训练,以美国脊髓损伤协会(ASIA)为主要评分指标,脊髓损伤步行指数(WISCI)和脊髓独立量表(SCIM)为次要评分指标。结果20例受试者的SCI平面分别位于C3~T11,平均受伤7年。治疗前,16例(80%)患者行走<10 m,18例(90%)患者自理生活需要协助。治疗后41~87周,受试者ASIA运动评分无明显变化,而WISCI和SCIM评分明显提高。15例(75%)患者可在辅助下步行10 m,12例(60%)患者恢复膀胱和肠道控制,5例(25%)患者由完全性SCI变为不完全性SCI;所有患者无神经功能丢失。结论UCBMC移植和步行训练能提高慢性完全性SCI患者的WISCI和SCIM评分,但对运动评分没有改善,因此推测UCMBC移植能促进轴突的生长,从而激活中枢模式发生器,改善运动、排尿和排便等功能,而且联合使用MP和碳酸锂对细胞移植治疗无明显作用。Objective To assessing the safety,feasibility,efficacy and optimal cell dose of human leukocyte antigen(HLA≥4∶6)matched umbilical cord blood mononuclear cells(UCBMC)in the therapy of chronic complete spinal cord injury(SCI),and the effect of combined use of methylprednisolone(MP)and lithium carbonate on cell transplantation.Methods Twenty patients with SCI admitted to Department of Neurosurgery of 920 Hospital of Joint Logistics Support Force from February 2011 to January 2014 were selected and divided into 5 groups(group A,B,C,D,E)according to the random number table method,with 4 subjects in each group.UCBMC was injected at 4 points(2 points in each side)at the upper and lower edge of the injured spinal nerve.Group A,group B and group C were injected with 4,8 and 16μL(100000 UCBMC/μL,6.4 million cells)to the upper and lower dorsal root of SCI,group D received 16μL cell injection plus 30 mg/kg MP intravenous injection,group E received 16μL cell injection plus MP and 6-week oral lithium carbonate(750 mg/d).The subjects underwent intensive walking training for 3-6 months.The primary outcome was American Spinal Injury Association(ASIA)scores.Secondary outcomes include walking index of spinal cord injury(WISCI)and spinal cord independence measure(SCIM).Results Twenty subjects averaged 7 years after C3-T11 SCI.Before treatment,16 subjects(80%)could not walk 10 m even with assistance,and 18 subjects(90%)need assistance for bladder or bowel care.At 41-87 weeks,ASIA motor scores did not change but WISCI and SCIM scores improved.Fifteen subjects(75%)could walk 10 m with assistance,12 subjects(60%)did not need assistance for bladder care or bowel care,5 subjects converted from complete to incomplete.Meanwhile none of subjects lost further neurological functions.Conclusion UCBMC and locomotor training improved WISCI and SCIM but not motor scores.We hypothesize that UCMBC transplants stimulate growth of axons that activate central pattern generators for locomotion,micturition,and defecation.Combined use of MP and li

关 键 词：脊髓损伤 脐血单核细胞 移植 

分 类 号：R651.2[医药卫生—外科学]