Effects of human mesenchymal stem cells on the differentiation of dendritic cells from CD34+ cells
Effects of human mesenchymal stem cells on the differentiation of dendritic cells from CD34+ cells
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DOI：
10.1089/scd.2007.0065
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发表时间：
2007-10-01
影响因子：
4
通讯作者：
Zhao, Robert Chunhua
中科院分区：
文献类型：
--
作者：
Chen, Lei;Zhang, Wei;Zhao, Robert Chunhua
间充质干细胞（MSC）在体外和体内均具有深远的免疫调节功能。然而，它们对树突状细胞（DC）分化的影响尚不清楚。在本研究中，我们采用体外模型来研究人类 MSC 对 DC 发育的影响。从脐带血中分离的CD34(+)细胞在常规DC(cDC)或浆细胞样DC(pDC)分化条件下、在存在或不存在MSC或其条件培养基的情况下培养。在这里，我们表明，间充质干细胞及其条件培养基在任一条件下都显着增加了产生的细胞数量。在 MSC 或其条件培养基存在下，具有 cDC 表型的细胞百分比显着降低，而 pDC 的百分比则增加。来自MSCs或其条件培养基处理的CD34(+)细胞的cDC刺激同种异体T细胞的能力被削弱。此外，MSC 可以使 DC 功能从 cDC 转向 pDC，从而使免疫系统偏向 Th2 反应，远离 Th1 反应。阻断 MSC 的前列腺素 E-2 (PGE(2)) 合成可以逆转 MSC 对 DC 分化和功能的大部分影响。因此，MSC 可以通过 PGE(2) 的产生显着影响 DC 的发育。
Mesenchymal stem cells (MSCs) have profound immunomodulatory functions both in vitro and in vivo. However, their effects on the differentiation of dendritic cells (DCs) are unknown. In this study, we employed an in vitro model to investigate the effects of human MSCs on the development of DCs. CD34(+) cells isolated from cord blood were cultured under conventional DC(cDC) or plasmacytoid DC (pDC) differentiation conditions, in the presence or absence of MSCs or their conditioned medium. Here we show that both MSCs and their conditioned medium dramatically increased the numbers of cells generated under either condition. The percentage of cells with the cDC phenotype is significantly reduced in the presence of MSCs or their conditioned medium, whereas the percentage of pDC increased. The capacity of cDCs from MSCs or their conditioned medium-treated CD34(+) cells to stimulate allogeneic T cells was weakened. Furthermore, MSCs can skew the DC function from cDC to pDC, thus biasing the immune system toward Th2 and away from Th1 responses. Blocking the prostaglandin E-2 (PGE(2)) synthesis of MSCs can reverse most of these influences of MSCs on DCs differentiation and function. Therefore, MSCs can significantly influence DC development through PGE(2) production.