摘要
背景:尽管中枢神经系统是"免疫特赦区",但有研究显示出宿主对神经干细胞存在排斥,从临床安全性考虑,加深神经干细胞移植免疫学的研究极其必要。目的:研究肌萎缩侧索硬化患者神经干细胞移植后中枢内的体液免疫反应模式。设计:病例分析。对象:2006-09/2007-06武装警察部队总医院收治的肌萎缩侧索硬化患者32例,均符合EL Escorial诊断标准,经影像学和Queckenstedt试验确定不存在蛛网膜下腔阻塞,男21例,女11例,平均年龄(51±10)岁,其中有8例曾于6个月前行1个疗程神经干细胞移植治疗。神经干细胞取自流产胎儿的脑组织,产妇及家属均签署捐赠同意书,实验经医院医学伦理委员会批准。方法:1个疗程共行4次神经干细胞移植,每次移植所分离培养的神经干细胞4.0×106个,1次/周,其中3次经腰穿途径,1次经脑实质内移植途径。于首次移植前和末次移植后分别配对采取脑脊液和晨起空腹血清各2mL,用散射比浊法平行测定配对脑脊液和血清中的白蛋白、IgG、IgA、IgM浓度。主要观察指标:以脑脊液/血清白蛋白浓度商来反映血-脑脊液屏障功能,检测免疫球蛋白鞘内合成率。结果:与细胞移植前比较,移植后32例患者脑脊液/血清白蛋白浓度商均明显增加(P<0.05),脑脊液中IgG、IgA、IgM浓度均显著升高(P<0.05)。移植前32例患者各类免疫球蛋白鞘内合成率均<0,未发现鞘内免疫球蛋白合成;移植后1例女性患者IgA鞘内合成率为24.3%,1例男性患者IgM鞘内合成率为7.0%,余30例患者仍未发现有鞘内免疫球蛋白合成。结论:脑脊液内免疫球蛋白浓度升高是因脑脊液/血清白蛋白浓度商升高引起而非鞘内合成,植入物并未引起可以探测到的中枢内体液免疫反应。
BACKGROUND: The central nervous system is a "immune special pardon region", but some studies showed that the host is against neural stem cells. From the aspects of clinical safety, to deepen immunological study of neural stem cell transplantation is extremely necessary. OBJECTIVE: To investigate the humoral immune response pattern for amyotrophic lateral sclerosis (ALS) patients after neural stem cell transplantation. DESIGN: Case analysis. PARTICIPANTS: Totally 32 patients suffered from ALS were recruited at the General Hospital of Chinese People's Armed Police from September 2006 to June 2007 according to the EL Escorial Criteria, including 21 males and 11 females, averagely aged (5 1±10) years. None of them developed subarachnoid occlusion. Eight patients received neural stem cell transplantation for 1 course 6 months this study. Neural stem cells were harvested from brain tissues of aborted fetus. Informed consent was obtained from parturients and their family members. This study was approved by Hospital's Ethical Committee. METHODS: Every patient received neural stem cell transplantation, once a week, 4 times in total, at a density of 4.0×10^6 once. Using lumbar puncture in three times transplantation, and brain parenchyma once. Paired 2 mL cerebrospinal fluid and 2 mL fasting serum in the morning samples were obtained before the first and after the last transplantation. Albumin, IgG, IgA, IgM concentrations in every paired cerebrospinal fluid-serum sample were tested MAIN OUTCOME MEASURES: Albumin cerebrospinal fluid/Serum Quotient (QAIb) (reflecting blood-cerebrospinal fluid barrier function) and immunoglobulin intrathecal fractions. RESULTS: QAlb significantly increased after transplantation compared with that before transplantation (P 〈 0.05). Cerebrospinal fluid IgG, IgA, IgM concentrations significantly increased (P 〈 0.05). There was no immunoglobulin intrathecal synthesis in most patients (30/32) due to intrathecal fractions〈0, 1 female with IgA intrathecal synthesis (IgAIF=24.3%), 1 male with IgM intrathecal synthesis (IgMIF=7.0%). CONCLUSION: The increased cerebrospinal fluid immunoglobulin concentrations after transplantations were due to the increased QAlb, but not intrathecal synthesis. The grafts did not evoke detectable humoral immune response in the central nervous system.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2008年第38期7439-7442,共4页
Journal of Clinical Rehabilitative Tissue Engineering Research
基金
教育部新世纪优秀人才支持计划(NCET-06-1083)~~