间充质干细胞治疗强直性脊柱炎的临床研究

发布时间：2019-03-10 20:50

【摘要】：研究背景：强直性脊柱炎(AS)是一种脊柱关节疾病,主要以骶髂关节炎、外周炎症关节病及中轴脊柱关节病变为特点的慢性进行性炎症性疾病,可伴随眼、肺、心血管、肾脏、神经系统等脏器损害。其致病机制主要是免疫紊乱介导的炎性反应。患者都有腰背部疼痛及关节活动受限。诊断主要依靠1984年纽约修订的强直性脊柱炎诊断标准。目前主要依靠药物治疗,包括非甾体抗炎药、柳氮磺砒啶、糖皮质激素、肿瘤坏死因子抑制剂。针对外周关节活动受限及关节强直主要依靠手术治疗。而康复训练也随着对AS的认识的深入而被逐渐重视。研究目的：研究间充质干细胞输注治疗强直性脊柱炎的安全性及疗效的研究。资料与方法：1.资料：本组收集5例强直性脊柱炎患者,符合强直性脊柱炎诊断诊断标准(1984年纽约修订的强直性脊柱炎诊断标准)；年龄在18至60岁之间；入组前若服用非甾体抗炎药、甲氨蝶呤、柳氮磺砒啶、羟氯喹、小剂量激素,则剂量至少稳定4周以上。5例患者均为非妊娠或哺乳期妇女,均无器官衰竭、艾滋病、肝炎、结核或者其他中毒感染或者精神病,均无对人血白蛋白和间充质干细胞(Mesenchymal stem cell, MSC)培养体系主要成分如青霉素、链霉素过敏者。入组后对患者进行评估,评估内容如下：体格检查、Bath强直性脊柱炎活动性指数(BASDAI)、Bath强直性脊柱炎功能指数(BASFI)、Bath强直性脊柱炎测量指数(BASMI)评估；血沉、C反应蛋白、血常规、尿常规、肝肾功能检测；影像学等检测。2.方法：间充质干细胞培养,诱导间充质干细胞分化,流式细胞术对间充质干细胞表面分子检测,细菌(需氧菌培养、厌氧菌培养)、支原体和内毒素检测合格的MSC方可应用于受试患者。患者入组后,给予间充质干细胞输注治疗,剂量为lIU/10Kg(1IU=1×107个间充质干细胞),每个病人平均输注1-2次。病人在输注后均给予疗效评估及安全性评价,包括：体格检查、BASDAI、BASFI、 BASMI评估；血沉、C反应蛋白、血常规、尿常规、肝肾功能检测；影像学等检测及不良反应记录。并与治疗前进行对比,已达到评价疗效的目的。结果：1.本组5名患者输注后3名出现发热,体温在38.5-39℃之间,1例患者体温达到39℃以上,给予地塞米松5mg肌肉注射或口服非甾体类药物处理治疗,2-6小时后体温降至正常范围内。2.患者治疗前及治疗后疗效对比：患者BASDAI、BASMI评分有不同程度的下降,BASFI评分有所上升,血沉及C反应蛋白有所下降,症状较前均有所好转。结论：间充质干细胞输注治疗强直性脊柱炎患者是安全的,具有较好的耐受性,并有效降低了炎性指标,改善了患者脊柱和关节的活动功能和生活质量。
[Abstract]:Background: ankylosing spondylitis (AS) is a disease of the spine and joint, characterized mainly by sacroiliac arthritis, peripheral inflammatory arthropathy and mid-axis spondyloarthropathy, which can be associated with eye, lung and cardiovascular diseases. Kidney, nervous system and other organs damage. Its pathogenesis is mainly immune disturbance mediated inflammatory response. All patients have low back pain and limited joint movement. The diagnosis relies mainly on the diagnostic criteria for ankylosing spondylitis revised in New York in 1984. Currently, drug therapy, including non-steroidal anti-inflammatory drugs, sulfasalazine, glucocorticoids, tumor necrosis factor inhibitors. For peripheral joint mobility limitation and ankylosis, surgical treatment is mainly needed. With the deepening of the knowledge of AS, rehabilitation training has been paid more and more attention. Objective: to study the safety and efficacy of mesenchymal stem cells (MSCs) infusion in the treatment of ankylosing spondylitis (ankylosing spondylitis). Information and methods: 1. Materials: five cases of ankylosing spondylitis were collected, which met the diagnostic criteria of ankylosing spondylitis (the diagnostic criteria of ankylosing spondylitis revised in 1984 in New York), aged from 18 to 60 years old, and the age of ankylosing spondylitis ranged from 18 to 60 years old. If non-steroidal anti-inflammatory drugs, methotrexate, sulfasalazine, hydroxychloroquine, low-dose hormone were taken before entering the group, the dose was stable for at least 4 weeks. All 5 patients were non-pregnant or lactating women without organ failure, AIDS and hepatitis. Tuberculosis or other toxic infections or psychosis have no major components such as penicillin or streptomycin allergies to human albumin and mesenchymal stem cell (Mesenchymal stem cell, MSC) culture systems. The results were as follows: physical examination, Bath Ankylosing Spondylitis activity Index (BASDAI), Bath), Ankylosing Spondylitis activity Index (BASDAI), Bath), Ankylosing Spondylitis function Index (BASFI), Bath), Ankylosing Spondylitis Measurement Index (BASMI); Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), blood routine, urine routine, liver and kidney function, imaging and so on. Methods: mesenchymal stem cells were cultured to induce differentiation of mesenchymal stem cells, surface molecules of mesenchymal stem cells were detected by flow cytometry, bacteria (aerobic culture, anaerobic culture), Mycoplasma and endotoxin detection of qualified MSC can be used in patients tested. The patients were treated with lIU/10Kg (1IU=1 脳 10 ~ 7 mesenchymal stem cells) at an average dose of 1 ~ 2 times per patient. All patients were evaluated for efficacy and safety after infusion, including physical examination, BASDAI,BASFI, BASMI evaluation, erythrocyte sedimentation rate, C-reactive protein, blood routine, urine routine, liver and kidney function test, imaging examination and adverse reaction record. And compared with before treatment, has achieved the purpose of evaluating curative effect. Results: 1. Three of the 5 patients developed fever after infusion, the body temperature was between 38.5 鈩，

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