中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (10): 1885-1891.doi: 10.3969/j.issn.1673-8225.2010.10.038

• 干细胞临床实践 clinical practice of stem cells • 上一篇    下一篇

骨髓间充质干细胞移植治疗硬皮病样慢性移植物抗宿主病： 4例免疫机制变化

周 虹1，郭 梅2，孙琪云2，黄 姗1，杨 卓1，边春景1，曾 洋1，艾辉胜2，赵春华1   

  1. 1北京协和医学院，中国医学科学院组织工程中心，北京市 100005；
    2解放军军事医学科学院附属307医院血液病移植科，北京市 100039
  • 出版日期:2010-03-05 发布日期:2010-03-05
  • 通讯作者: 赵春华，博士，教授，博士生导师，北京协和医学院，中国医学科学院组织工程中心，北京市 100005
  • 作者简介:周 虹，女，1981年生，河北省唐山市人，汉族，北京协和医学院在读博士，主要从事干细胞的基础研究与临床应用。 comeoniris@ yahoo.com.cn

Bone marrow mesenchymal stem cells transplantation for the treatment of sclerodermatous chronic graft-versus-host disease: Immunologic mechanism changes in 4 cases

Zhou Hong1, Guo Mei2, Sun Qi-yun2, Huang Shan1, Yang Zhuo1, Bian Chun-jing1, Zeng Yang1, Ai Hui-sheng2, Zhao Chun-hua1   

  1. 1Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing  100005, China;
    2Department of Hematology and Transplantation, Affiliated 307th Hospital of Academy of Military Medicine Science, Beijing  100039, China
  • Online:2010-03-05 Published:2010-03-05
  • Contact: Zhao Chun-hua, Doctor, Professor, Doctoral supervisor, Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
  • About author:Zhou Hong, Studying for doctorate, Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China comeoniris@yahoo. com.cn

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摘要：

背景：骨髓间充质干细胞由于具有免疫调节能力使其能用于治疗移植物抗宿主病，特别是治疗急性移植物抗宿主病已获临床成功，但是对于治疗慢性移植物抗宿主病，特别是硬皮病样慢性移植物抗宿主病(ScGVHD)的研究报道还很少。

目的：评价骨髓间充质干细胞治疗ScGVHD的有效性及安全性，同时探讨取得疗效的免疫学机制。

方法：于2006-09/2008-08在解放军307医院血液移植科接受骨髓间充质干细胞髓内注射ScGVHD患者4例，男3例，女1例；中位年龄41岁。骨髓间充质干细胞髓内注射具体方法：取右髂前上棘为穿刺注射点，注射骨髓间充质干细胞悬液，4例患者的给药剂量基本控制在(1.0~2.0)×107个细胞/次，行间断多次给药。合并用药亦有差异，但都为治疗ScGVHD的传统药物，且用量大为减少。

结果与结论：经过多次骨髓内输注骨髓间充质干细胞后，Th细胞的比例发生了明显的变化，Th1的比例上调，Th2的比例相应的下调，从而使两者达到了新的平衡点。与之相应，患者的临床症状也逐渐好转。而且在骨髓间充质干细胞治疗的随访期内，患者的生命体征和实验室检查指标均未发现异常，也未出现白血病的复发。证明骨髓间充质干细胞对ScGVHD是有治疗效果的，为临床治疗ScGVHD开辟了一个新的方法，从而能提高白血病患者骨髓移植的存活率。但由于样本数较少，需要进一步扩大规模进行临床研究，以进一步证实其安全性和疗效。

关键词: 慢性移植物抗宿主病, 硬皮病样慢性移植物抗宿主病, 免疫机制, 骨髓间充质干细胞, 干细胞

Abstract:

BACKGROUND: The immunomodulatory ability of bone marrow mesenchymal stem cells (BMSCs) gives it a promising future in treating graft-versus-host disease (GVHD), especially with previous success in treating patients with acute GVHD. However, there are fewer reports concerning BMSCs in treating chronic GVHD, particularly for sclerodermatous chronic graft-versus-host disease (ScGVHD).

OBJECTIVE: To evaluate the efficacy and safety of treatment of BMSCs for ScGVHD, and to primarily explore the immunological mechanism of clinical efficacy.

METHODS: Four ScGVHD patients at the Affiliated Hospital of Academy of Military Medicine Science, between September 2006 and August 2008, were enrolled for this trial. The median patient age was 41 years, 1 female and 3 male. The patients received BMSCs infusion at a dose of (1.0-2.0)×107 cells every time by intrabone marrow injection from the anterosuperior iliac spine and BMSCs from the same donor for the same patient were infused more than once. Concomitant medications for ScGVHD were individualized for each patient, but all were current standard medicines and the doses were significantly tapered.

RESULTS AND CONCLUTION: After BMSCs infusion, the ratio of Th1 to Th2 was dramatically overturned, with an increase of Th1 and a decrease of Th2 reaching at a new balance. Correspondingly, symptoms of all the four patients gradually improved. During the course of BMSCs treatment, the life signs and laboratory results from the recipients remained normal. By the time of this report, there has been no recurrence of leukemia in the four patients. Although this study alone cannot guarantee the application of BMSCs in ScGVHD, the results are strongly in favor of the idea that the BMSCs treatment for ScGVHD patients is therapeutically practical without any detectable side effects, which may provide a new insight into the matter of treating ScGVHD clinically, thus will greatly increase the survival rate of leukemia after allogeneic bone marrow transplantation.

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