Reversal of serologic, immunologic, and histologic dysfunction in mice with systemic lupus erythematosus by long-term serial adipose tissue-derived mesenchymal stem cell transplantation
Reversal of serologic, immunologic, and histologic dysfunction in mice with systemic lupus erythematosus by long-term serial adipose tissue-derived mesenchymal stem cell transplantation
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DOI：
10.1002/art.33313
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Hong, Sung Hwa
中科院分区：
文献类型：
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作者：
Choi, Eun Wha;Shin, Il Seob;Hong, Sung Hwa
目的探讨人脂肪组织来源间充质干细胞（AD-MSC）移植治疗系统性红斑狼疮（SLE）的疗效，并确定疾病发生前后干细胞移植的最佳时间窗。(NZB从6周龄直到60周龄，每2周静脉内施用人AD-MSC（5 × 105），而对照组以相同的时间表接受盐水媒介物。另一个实验是在不同的开始时间点进行连续移植（6周龄或32周龄）。长期连续给药（共28次）人AD-MSCs改善SLE，无任何不良反应。与对照组相比，人AD-MSC治疗组具有显著更高的存活率，组织学和血清学异常以及免疫功能的改善，并且蛋白尿的发生率也降低。抗双链DNA抗体和血尿素氮水平显着下降与人AD-MSCs移植，和血清中的粒细胞-巨噬细胞集落刺激因子，白细胞介素-4（IL-4），IL-10水平显着增加。在人AD-MSC处理组的脾脏中观察到CD 4 + FoxP 3+细胞比例的显著增加和细胞因子产生能力的显著恢复。在第二个实验中，早期治疗组显示出比晚期治疗组更好的结果（更高的存活率和更低的蛋白尿发生率）。人AD-MSC系列移植治疗SLE有良好的效果，无不良反应。在发病前移植人AD-MSCs对改善SLE病情和恢复免疫稳态是有利的。
Objective To investigate the efficacy of human adipose tissuederived mesenchymal stem cell (AD-MSC) transplantation in systemic lupus erythematosus (SLE) and to determine the optimal transplantation window for stem cells either before or after disease onset.Methods. (NZB x NZW) F1 mice with SLE were administered human AD-MSCs (5 x 105) intravenously every 2 weeks from age 6 weeks until age 60 weeks, while the control group received saline vehicle on the same schedule. Another experiment was carried out with a different initiation time point for serial transplantation (age 6 weeks or age 32 weeks).Results. Long-term serial administration (total of 28 times) of human AD-MSCs ameliorated SLE without any adverse effects. Compared with the control group, the human AD-MSC-treated group had a significantly higher survival rate with improvement of histologic and serologic abnormalities and immunologic function, and also had a decreased incidence of proteinuria. Anti-double-stranded DNA antibodies and blood urea nitrogen levels decreased significantly with transplantation of human AD-MSCs, and serum levels of granulocyte-macrophage colony-stimulating factor, interleukin-4 (IL-4), and IL-10 increased significantly. A significant increase in the proportion of CD4+FoxP3+ cells and a marked restoration of capacity for cytokine production were observed in spleens from the human AD-MSC-treated group. In the second experiment, an early stage treatment group showed better results (higher survival rates and lower incidence of proteinuria) than an advanced stage treatment group.Conclusion. Serial human AD-MSC transplantation had beneficial effects in the treatment of SLE, without adverse effects. Transplantation of human AD-MSCs before disease onset was preferable for amelioration of SLE and restoration of immune homeostasis.