Mesenchymal stromal cells of bone marrow and azathioprine in Crohn's disease therapy
Mesenchymal stromal cells of bone marrow and azathioprine in Crohn's disease therapy
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DOI：
10.26442/terarkh201890247-52
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发表时间：
2018-01-01
影响因子：
0.3
通讯作者：
Parfenov, A. I.
中科院分区：
文献类型：
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作者：
Knyazev, O. V.;Kagramanova, A. V.;Parfenov, A. I.
克罗恩病(CD)是一种病因不明的慢性反复发作的胃肠道疾病。CD治疗的新方法之一是使用干细胞，特别是间充质基质细胞(MSCs)。目前，在接受其他免疫调节药物同时治疗的患者中，正在研究在临床实践中使用MSC治疗慢性炎症性和自身免疫性疾病。目的：评价硫唑嘌呤(AZA)对骨髓间充质干细胞(MSCs)治疗CD的疗效。这项研究包括34名炎症性疾病患者(Lumina！)CD的形式。第1组(n=15)采用MSCs培养联合AZA抗炎治疗。第2组(n=19)接受不含AZA的MSCs。根据克隆氏病活动性指数(CDAI)积分评估发作的严重程度。治疗后2、6、12个月分别检测免疫球蛋白(IgA、Ig G、Ig M)、白介素1β(IL 1β)、白介素1β(IL 1β)、肿瘤坏死因子-α(INF-α)、干扰素-γ(INF-γ)、转化生长因子-1β(TGF-1β)、C反应蛋白(CRP)、血小板和血沉。第1组的初始CDAI值为337.6+/-17.1分，第2组为-332.7+/-11.0分(P=0.30)。两组患者治疗2个月后CDAI均显着下降。骨髓间充质干细胞：第1组为118.9+/-12.4分，第2组为-120.3+/-14.1分(P=0.70)，6个月后分别为-110.3+/-11.1分和114.3+/-11.8分(P=0.8)。治疗12个月后，第1组CDAI值为99.9+/-10.8分，第2组为100.6+/-12.1分(P=0.80)。病史越长、ASA病程越长的患者，其血清IgA、Ig G、Ig M水平越低。加入MSC后，两组BC患者的促炎细胞因子和抗炎细胞因子均有增加趋势，第1组促炎细胞因子-干扰素-γ、干扰素-α、IL-1β水平明显降低，提示MSCs和AZA的免疫抑制作用增强，具有更明显的抗炎作用。骨髓间充质干细胞移植可促进CD患者血清中免疫球蛋白、细胞因子浓度的升高，并随着临床缓解的开始而恢复其平衡。与AZA联合使用有更明显的抗炎作用。
Crohn's disease (CD) is a chronic, recurring disease of the gastrointestinal tract of unclear etiology. One of the new approaches to CD therapy is the use of the possibilities of stem cells, in particular, mesenchymal stromal cells (MSCs). Currently, the use of MSC in clinical practice for the treatment of chronic inflammatory and autoimmune diseases is being studied in patients who receive concomitant therapy with other immunomodulatory medications.Aim. To evaluate the effectiveness of MSCs therapy in patients with CD receiving azathioprine (AZA).Materials and methods. The study included 34 patients with inflammatory (lumina!) form of CD. The 1st group of patients (n=15) received anti-inflammatory therapy using MSCs culture in combination with AZA. The 2nd group (n=19) received MSCs without AZA. The severity of the attack was assessed in points in accordance with the of Crohn's disease activity index (CDAI). Immunoglobulins (IgA, IgG, IgM), interleukins (IL) 1 beta, 4, 10, tumor necrosis factor-alpha (INF-alpha), interferon-gamma (INF-gamma), transforming growth factor-1 beta (TGF-1 beta), C-reactive protein (CRP), platelets and erythrocyte sedimentation rate (ESR) at 2, 6 and 12 months from the beginning of MSCs therapy.Results. The initial mean CDAI in the 1st group was 337.6 +/- 17.1 points, in the 2nd group - 332.7 +/- 11.0 points (p=0.3). In both groups of patients there was a significant decrease in CDAI after 2 months. From the beginning of therapy MSCs: in the 1st group to 118.9 +/- 12.4 points, in the 2nd - 120.3 +/- 14.1 points (p=0.7), after 6 months-110.3 +/- 11.1 and 114.3 +/- 11.8 points (p=0.8), respectively. After 12 months CDAI in the 1st group was 99.9 +/- 10.8 points, in the 2nd group it was 100.6 +/- 12.1 points (p=0.8). The level of IgA, IgG, IgM was significantly lower in the group of patients with a longer history of the disease and long-term ASA. After the introduction of MSC in both groups of patients with BC, there was a tendency for the growth of pro- and anti-inflammatory cytokines, with a significantly lower level of pro-inflammatory cytokines - INF-gamma, INF-alpha, IL-1 beta - in the 1st group, indicating potentiation of the immunosuppressive effect of MSCs and AZA, which provides a more pronounced anti-inflammatory effect.Conclusion. Transplantation of MSCs promotes an increase in the serum of patients with CD initially reduced concentration of IG, cytokines and restoring their balance as the onset of clinical remission. The combination with AZA has a more pronounced anti-inflammatory effect.