利用异体间充质干细胞移植改变多发性硬化症临床病程的疗法对患者免疫参数的影响

Q4 Medicine
A. S. Fedulov, M. M. Zafranskaya, A. V. Borisov, D. B. Nizhegorodova, N. A. Volkova, S. I. Krivenko, T. A. Shalukho
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引用次数: 0

摘要

多发性硬化症(MS)是一种多因素的自身免疫性神经系统慢性疾病,表现为多灶性神经系统症状,在典型病例中出现复发症状。MS是现代神经病学的难题之一,其特点是疾病流行,患者患病率在20 ~ 40岁年龄组,致残率高。MS治疗方案的主要目标是免疫系统的出现,以抑制导致脱髓鞘的炎症过程。使用一组可以在临床上改变MS病程的药物(β -干扰素、醋酸格拉替默、芬戈莫德等),40%的患者疗效良好,40%的患者疗效可疑,20%的MS患者没有检测到治疗。缺乏针对选择性刺激抑制自身反应性t淋巴细胞克隆和恢复中枢神经系统受损区域的治疗方案,削弱了对间充质干细胞(MSCs)免疫调节和神经保护特性的日益增长的兴趣。从携带者的角度来看,同种异体与自体间充质干细胞移植的益处被广泛讨论,但在获得多发性硬化症方面,没有客观证据表明一种细胞疗法比自体或同种异体移植的估计和估计费用更有优势,这仍然存在争议。目的:探讨同种异体间充质干细胞修饰疗法对多发性硬化症患者免疫指标的影响。4例复发缓解型多发性硬化症患者的一些免疫生物标志物动态评估结果,所有患者为男性。中位年龄为35.0 + 11.4岁。筛查期间,扩展残疾状态量表(EDSS)评分为3.6 [2.5;6.0]。7个供体的骨髓间充质干细胞的免疫和细胞形态学参数均因脂肪组织(AT)而增强。在7份AT MSCs样本中,选择抑制t淋巴细胞增殖系数最高的2份样本,其中4份应采用生物医学细胞制品进行治疗。在MS患者中,在移植后6个月观察到最显著的变化,其特征是γIFN的产生减少,未成熟的“双阳性”和“双阴性”t淋巴细胞的功能数量减少。具有γδ t细胞受体的t淋巴细胞的细胞毒性取向降低,其特征是表达CD45RO+(记忆细胞标志物)的细胞数量增加,而表达γδ tcr CD314+淋巴细胞(杀伤受体表达关键激活因子)的细胞数量减少。一项将alloMSCs移植到多发性硬化症患者免疫状态的研究的初步结果表明,他们在此应用中接受疾病修饰治疗作为发病、疾病修饰治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Impact of the therapy that changes the clinical course of multiple sclerosis using allogeneic mesenchymal stem cell transplantation on the immunological parameters of patients
Multiple sclerosis (MS) is a multifactorial, autoimmune, chronic disease of the nervous system, manifested by multifocal neurological symptoms and occurring in typical cases in the presence of symptoms of a relapsing course. MS is one of the problems of modern neurology, which is characterized by the prevalence of diseases, the prevalence of patients in the age group from 20 to 40 years, as well as high disability. The main target of therapeutic options in MS is the appearance  on the immune system in order to suppress the inflammatory process leading to demyelination. With a set of drugs that allow clinically modifying the course of MS (beta-interferon, glatiramer acetate, fingolimod, etc.), 40 % of patients have a good effect, 40 % have a questionable result, and 20 % of patients with MS do not detect treatment. Lack of treatment protocols aimed at selective stimulatory suppression of autoreactive T-lymphocyte clones and restoration of affected areas of the CNS, weakening of the ever-increasing interest in identifying the immunomodulatory and neuroprotective properties of mesenchymal stem cells (MSCs). From carriers, the benefits of allogeneic versus autologous MSC implantation are widely discussed without the presence of objective evidence of the superiority of one type of cell therapy over the estimated and estimated fees of autologous or allogeneic transplants in obtaining MS remains controversial.Objective ‒ to study the effect of modifying therapy using allogeneic mesenchymal stromal stem cells on the immunological parameters of patients with multiple sclerosis.The results of assessing the dynamics of a number of immunological biomarkers in 4 patients with relapsing-remitting MS. All patients are men. The median age is 35.0 + 11.4 years. At the screening period, the Expanded Disability Status Scale (EDSS) score was 3.6 [2.5; 6.0]. immunological and cellular-morphological parameters of MSC cultures were revealed, enhanced due to adipose tissue (AT) of 7 donors. Of the 7 samples of AT MSCs, 2 samples were selected with the highest coefficients of suppression of T-lymphocyte proliferation, of which 4 biomedical cell products should be taken for therapy.In patients with MS, the most significant changes were observed by 6 months of the post-transplantation period and were characterized by a decrease in γIFN production, the number of functions of immature “double positive” and “double negative” T-lymphocytes, and a decrease in the cytotoxic orientation of T-lymphocytes with a γδ T-cell receptor characterized by characteristics of an increase in the number of cells expressing CD45RO+ (memory cell marker) in an increase with a decrease in the number of γδTCR CD314+ lymphocytes (expressive key activator of killer receptors).Preliminary results from a study of transplantation of alloMSCs to the immunological status of MS patients suggest that they accept disease-modifying therapy in this application as pathogenetic, disease-modifying therapy.
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