【作者】 吴宗辉；

【导师】 虞乐华；

【作者基本信息】 重庆医科大学 ， 康复医学与理疗学， 2011， 硕士

【摘要】 目的脊髓损伤(SCI)严重威胁人类健康,给家庭和社会带来沉重负担。对SCI的治疗包括外科手术、药物治疗以及康复训练等,但均作用有限。近年来,干细胞的临床应用给SCI的治疗带来了新希望,其相关研究备受关注。研究表明,骨髓间充质干细胞(MSCs)对SCI患者造成的神经功能缺失具有治疗作用,而自体MSCs有取材方便、无免疫排斥反应、不存在伦理道德问题等优点,已成为了研究的热点。但临床尚缺乏足够资料证实其疗效。本文首次报道采用自体MSCs经根动脉和蛛网膜下腔移植法治疗SCI患者,观察比较研究2种治疗方法的近期治疗效果以及治疗安全性。方法选择经CT或MRI确诊并行手术或非手术治疗、暴力引起的、病程1月～2年、年龄15岁～60岁之间、无昏迷及其他并发症、能至少接受标准康复治疗一月、自愿并签署知情同意书的SCI患者26例,其中16例除做标准康复治疗外,接受干细胞移植治疗(8例为经根动脉途径移植治疗组,简称根动脉组;8例为经蛛网膜下腔途径移植治疗组,简称蛛网膜下腔组),10例为只做标准康复治疗的对照组病例。所有受试者标准康复治疗时间为一月,感觉、运动功能评定采用美国脊柱损伤协会(ASIA)与国际脊髓学会(ISCoS)制定的脊髓损伤神经学分类国际标准(第六版,2006)进行评定。两组在年龄、性别、病程、损伤程度等方面无统计学差异(均p>0.05),具有可比性。根动脉组与蛛网膜下腔组在标准康复治疗的基础上给予自体MSCs移植治疗,经髂骨穿刺采集自体骨髓,分离提取后经根动脉或蛛网膜下腔注入;对照组仅给予常规标准的康复治疗。根动脉组与蛛网膜下腔组于移植术前和后一月、对照组于标准康复治疗前和后一月进行运动与感觉神经功能评分、日常生活活动能力(ADL)评定。由两名非参与治疗的且经过专业训练的医师进行评估。结果1)、神经功能评分变化:治疗后一月和治疗前相比,根动脉组患者浅感觉、深感觉及运动功能评分有改善,统计学处理后差异有显著性(均p<0.01);蛛网膜下腔组患者运动功能评分有改善,统计学处理后差异有显著性(p<0.01);对照组患者浅感觉评分有所改善,统计学处理后差异有显著性(p<0.05)。2)、日常生活活动能力(ADL)评分:治疗后一月与治疗前相比,根动脉组与蛛网膜下腔组患者的ADL评分均提高,差异有统计学意义(均p<0.05);对照组ADL评分统计学差异没有显著性(P>0.05)。3)、不同治疗途径的治疗效果比较:治疗后一月将根动脉组、蛛网膜下腔组与对照组之间的治疗效果进行比较,根动脉组和蛛网膜下腔组的浅深感觉、运动功能评分统计学处理差异没有显著性(均P>0.05);三组ADL评分统计学差异没有显著性(P>0.05);根动脉组与蛛网膜下腔组之间进行比较,浅深感觉、运动功能、ADL评分统计学差异也没有显著性(P>0.05)。4)、不良反应:有1例经蛛网膜下腔治疗患者发生了术后的发热,原因不明,肌肉注射地塞米松后缓解,无复发。根动脉组患者未有任何不良反应出现。结论自体MSCs经根动脉或蛛网膜下腔移植治疗SCI,术后一月患者的浅深感觉、运动功能及ADL评分有所改善,未有严重副反应发生,其中经根动脉途径移植治疗SCI为首次报道。临床初步研究表明:自体MSCs移植治疗SCI有一定的近期临床疗效,操作简便,安全可行,值得做大样本双盲多中心的进一步临床研究与探索。目的初步观察自体骨髓间充质干细胞(MSCs)移植治疗脑神经损伤的临床效果和存在的问题。方法选取自愿并签署知情同意书的2例脑神经损伤患者(脑梗塞患者1例,脑干挫裂伤患者1例),首先抽取自体骨髓细胞悬液,在体外经过分离提取后,制成骨髓间充质干细胞悬液,经L4-5注入蛛网膜下腔,分离后剩余的血液立即经静脉回输给患者,术后常规标准康复治疗。采取手法肌力检查(MMT)进行肌力评定分级,日常生活活动能力(ADL)评定采用Barthel指数评分,偏瘫分级采用Brunnstrom偏瘫运动分级标准。结果脑梗塞患者(病例1)自体移植MSCs术后1月功能评定无明显变化。脑干挫裂伤患者(病例2)自体移植MSCs术后1月ADL评分提高10分,Brunnstrom偏瘫分级右下肢提升1级;术后3月ADL评分提高15分,右上肢肌力提升1级,Brunnstrom偏瘫分级右侧手指与上肢分别提升了1级。结论自体MSCs移植治疗脑神经损伤有一定的效果,本报告病例2的肌力评定、ADL评分、Brunnstrom偏瘫分级有所改善,治疗后无副反应发生。但是否真正为MSCs治疗所起的作用,还有待对比研究证实;对MSCs移植的时机、途径、个体差异、效果等还需更深入的研究与探讨。更多还原

【Abstract】 Objective SCI is not only a threat to human health, but also brings heavy burden for family and society. The main therapies for SCI are surgery, drugs, rehabilitation training and so on, but their effects are limited currently . In recent years, stem cells therapy for SCI brings a light for SCI and it attracts more attention. Some studies have indicated that MSCs have a therapeutic effect on neurological deficit caused by SCI, meanwhile autologous MSCs without immunity rejection and ethic problem are more available therefore, it has become a focused research field. However, adequate clinical data of its effects are still lack.In this study we first report the autologous marrow mesenchymal stem cells transplantation through root artery and subarachnoid spaceto treat patients with SCI, and through observation we investigate the short-term curative effect and the safety of the two therapies.METHODS 26 SCI patients were enrolled in this study. They were diagnosed by CT or MRI and received surgical or conservative treatment, caused by violence, within 1-month to 2-year of SCI onset, age between 15 years to 60 years, with no coma or other complications, being able to get at least 1-month of standard rehabilitation, and were informed and had signed the informed consent document. Among the 26 enrolled patients, 16 received the stem cells transplantation as well as standard rehabilitation training (8 cases are the transplantation group through abbreviated as subarachnoid space group; another 8 are the transplantation group through root artery abbreviated as root artery group), and 10 patients were control group with standard rehabilitation therapy. The duration of standard rehabilitation treatment for all the enrolled patients was one month. Sensory and motor function assessments adopted the American Spinal Injury Association (ASIA) classification and degree of SCI were evaluated by International Standards for Neurological Classification of Spinal Cord Injury (Sixth Edition, 2006). There were no differences of age, duration of disease, degree of injury between the two groups (p>0.05). Both subarachnoid space group and root artery group were given autologous marrow mesenchymal stem cells transplantation therapy on the basis of comprehensive rehabilitation treatment. The autologous marrow was collected from iliac bone marrow puncture and injected through subarachnoid space and root artery after separation and extraction. The control group was given only conventional rehabilitation treatment. Both groups were received assessment of motor and sensory function and assessment of activities of daily living (ADL) on admission and one month after transplantation respectively; the control group received those assessments on admission and one month after rehabilitation treatment. The study was evaluated independently by two professional doctors who were not involved in the treatment.RESULTS 1)Change of neurological function scores: compared with admission,the root artery group had improvement in superficial, deep sensory and motor function scores in one month after transplantation, and there was a significant difference(p<0.01); The subarachnoid space group only had improvement in motor function scores, and there was a significant difference(p<0.01); The control group had improvement in superficial sensory function scores in one month after treatment, and there was a significant difference(p<0.05).2) Activities of daily living (ADL) score: The ADL scores of stem cells therapy group were all improved between on admission and one month after transplantation , and there was a significant difference (p<0.05); The ADL scores of control group had no significant difference (P>0.05).3) Comparisons on effect of different therapies: one month after treatment , to compare the different effects of subarachnoid space group, root artery group and control group, scores of superficial and deep sensory as well as motor functions patients in subarachnoid space group and root artery group looked like a better results than that of control group, but no significant difference (P>0.05); on ADL scores, patients in the three groups were nearly the same, and there was no significant difference (P>0.05); Compared between the two transplantation groups, patients had no significant difference on scores of superficial and deep sensory as well as motor functions(P>0.05).4) The adverse effects of stem cells transplantation: 1 patient got fever after transplantation through subarachnoid space, and the cause was unclear. The symptom relieved after giving intramuscular dexamethasone and there was no recurrence. No adverse effect was found in root artery group.CONCLUSION Using autologous MSCs transplantation through subarachnoid space and root artery to treat patients with SCI which was first reported, one month after operation the superficial and deep sensory, motor function as well as ADL scores of patients were improved, and there is no serious side effect. Autologous marrow stem cells transplantation has some short-term clinical effects for patients with SCI, and can be easily operated, it is safe and feasible, however, large sample, double-blind, multi-center clinical trials are further needed for evidence based medicine . Objective To explore the efficacy and clinical problems of autologous transplantation of marrow mesenchymal stem cells (MSCs) for treating patients with cranial nerve damage.METHODS 2 patients with cranial nerve damage treated by autologous transplantation of marrow mesenchymal stem cells were enrolled, who was volunteered and had signed the informed consent document. One was suffering from cerebral infarction,and the other was brainstem contusion and laceration. At first, extract autologous marrow cells suspension, and after isolation, make it as MSCs suspension; inject it into subarachnoid space through L4-5. The rest isolated blood was transfused back to patients through vein immediately. After operation, patients received conventional rehabilitation treatment. The grade of muscle strength was evaluated by MMT, ADL was assessed by Barthel, and hemiparalysis grade was evaluated by standard Brunnstrom stage.RESULTS The patient with cerebral infarction (case one) had no apparent change in functional evaluation one month after transplanting autologous MSCs. At the same time, one month after transplanting autologous MSCs the ADL score of the patient with brainstem contusion and laceration (case two) raised 10 points and Brunnstrom stage of right lower extremity raised 1 grade; in 3 month after operation, his ADL score raised 15 points, the muscle strength of right upper extremity increased 1 grade, and Brunnstrom stage of right upper extremity also raised 1 grade.CONCLUSION Autologous transplantation of marrow mesenchymal stem cells could be an effective method to treat patients with cranial nerve damage. The manual muscle, scores of ADL and Brunnstrom stage of the patient in case two of this report were equally improved, but it still needs to be identified whether the functional improvement was actually gotten from the stem cells therapy. Further studies are needed to explore the timing, paths, individual differences, clinical effects and so on of MSCs transplantation.更多还原