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溃疡性结肠炎患者的同种异体间充质基质细胞:两年观察

[Allogeneic mesenchymal stromal cells in patients with ulcerative colitis: two years of observation].

作者信息

Lazebnik L B, Kniazev O V, Konopliannikov A G, Parfenov A I, Ruchkina I N, Mikhaĭlova Z F, Tsaregorodtseva T M, Khomeriki S G, Rogozina V A, Gudkova R B, Shcherbakov P L, Konopliannikova O A

出版信息

Eksp Klin Gastroenterol. 2010(11):3-15.

Abstract

UNLABELLED

The aim of the study was to determine the efficacy and safety of mesenchymal stromal cells (MSCs) of bone marrow in the treatment of patients with ulcerative colitis (UC).

MATERIALS AND METHODS

The study included 44 patients with ulcerative colitis (UC), which was implemented MSC transplantation, 40 patients with UC who received standard therapy with mesalazane (salofalka) 4-6 g/day and corticosteroids (prednisone)--1-2 mg/kg, azathioprine--1.5 mg/kg methotrexate 20-50 mg/m2, and 12 patients who underwent induction and maintenance of infliximab therapy. 2-3 days prior to the induction of MSCs abolish immunosuppressive doses of corticosteroids reduced to 15-20 mg/day dose of aminosalicylates was left at 2.0 g/day. To quantify the results using the average values of indices of Rahmilevich clinical activity, indices of endoscopic and histological activity scales Mayo and Gebs. The patients were observed for 24 months after transplantation. Were studied parameters of the humoral immune status (immunoglobulin A, G, M, autologous antibody), cytokine profile. Bone marrow cells were obtained from the donor's sternum or the iliac crest. By culturing the end of 5 to 6 weeks received a population of allogeneic donor's MSCs in the amount of (1.5-2) x 10(8) cells needed for transplant patient. Culture of MSCs injected in the drip i/v, single dose.

RESULTS

In 34 (72.7%) patients with UC after the induction of MSCs was statistically significant compared with the group of patients treated with drugs only 5-aminosalicylic acid and corticosteroids, reducing the clinical and morphological indices of inflammatory activity. In 12 patients with UC include MSCs in the treatment program did not have a therapeutic effect. Application of MSC allowed to cancel corticosteroids in most patients with hormone-dependent and steroid resistance forms of UC, and in 7 to reduce the dose of prednisolone to 5 mg/day, limiting the use of drugs 5-ASA. According to the anti-inflammatory effectiveness of combined therapy with MSCs comparable to infliximab therapy.

CONCLUSION

The use of MSCs can be evaluated as a new strategic direction for therapy UC. MSC, introduced in I/O, have powerful immunomodulatory effects, reduce the activity of autoimmune inflammation and stimulate the reparative process in the intestinal mucosa, thereby increasing the duration of remission, reduces risk of recurrence of disease, reduces the frequency of hospitalizations.

摘要

未标注

本研究的目的是确定骨髓间充质基质细胞(MSCs)治疗溃疡性结肠炎(UC)患者的疗效和安全性。

材料与方法

该研究纳入了44例接受MSCs移植的溃疡性结肠炎(UC)患者、40例接受美沙拉嗪(莎尔福)4 - 6 g/天及皮质类固醇(泼尼松)1 - 2 mg/kg、硫唑嘌呤1.5 mg/kg、甲氨蝶呤20 - 50 mg/m²标准治疗的UC患者,以及12例接受英夫利昔单抗诱导和维持治疗的患者。在诱导MSCs前2 - 3天,将免疫抑制剂量的皮质类固醇减至15 - 20 mg/天,氨基水杨酸剂量维持在2.0 g/天。使用拉赫米列维奇临床活动指数、梅奥和格斯内镜及组织学活动量表指数的平均值来量化结果。移植后对患者进行24个月的观察。研究体液免疫状态参数(免疫球蛋白A、G、M、自身抗体)、细胞因子谱。骨髓细胞取自供体胸骨或髂嵴。通过培养5至6周后获得供体异基因MSCs群体,数量为(1.5 - 2)×10⁸个细胞,供移植患者使用。MSCs培养物通过静脉滴注注射,单次剂量。

结果

与仅接受5 - 氨基水杨酸和皮质类固醇治疗的患者组相比,34例(72.7%)接受MSCs诱导的UC患者炎症活动的临床和形态学指标有统计学意义的降低。12例将MSCs纳入治疗方案的UC患者未产生治疗效果。应用MSCs可使大多数激素依赖型和激素抵抗型UC患者停用皮质类固醇,7例患者将泼尼松龙剂量减至5 mg/天,限制了5 - ASA药物的使用。根据抗炎效果,MSCs联合治疗与英夫利昔单抗治疗相当。

结论

使用MSCs可被评估为治疗UC的一个新的战略方向。经静脉输入的MSCs具有强大的免疫调节作用,可降低自身免疫性炎症活动,刺激肠黏膜的修复过程,从而延长缓解期,降低疾病复发风险,减少住院频率。

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