Placenta-derived multipotent cells exhibit immunosuppressive properties that are enhanced in the presence of interferon-γ
Placenta-derived multipotent cells exhibit immunosuppressive properties that are enhanced in the presence of interferon-γ
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DOI：
10.1634/stemcells.2006-0071
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发表时间：
2006-11-01
期刊：
影响因子：
5.2
通讯作者：
Yen, B. Linju
中科院分区：
文献类型：
--
作者：
Chang, Chun-Jung;Yen, Men-Luh;Yen, B. Linju
几种类型的非造血干细胞，包括骨髓间充质干细胞（BMMSC）和胚胎干细胞，已被证明具有免疫抑制特性。我们发现，人胎盘来源的多能细胞（PDMCs），这是从一个没有伦理问题的来源分离，并具有多系分化潜力，具有很强的免疫抑制特性。PDMC抑制CD 4和CD 8群体中的有丝分裂原诱导的和同种异体淋巴细胞增殖。PDMCs的免疫抑制作用明显强于BMMSCs。PDMC和BMMSC均表达吲哚胺2，3-双加氧酶，但只有PDMC对细胞内人类白细胞抗原-G（HLA）呈阳性。从机制上讲，PDMC对淋巴细胞反应性的抑制不是由于细胞死亡，而是由于细胞增殖减少和调节性T细胞数量增加。添加白细胞介素-10和转化生长因子（TGF）-β的中和抗体可部分恢复淋巴细胞增殖。与BMMSC不同，用干扰素-γ处理3天的PDMCs仅非常轻微地上调HLA-DR。相反，PD-L1（一种在T细胞活化中起抑制作用的细胞表面标志物）上调，并且观察到TGF-β表达。PDMC的免疫抑制特性，沿着其多谱系分化潜力、易于获得和丰富的细胞数量，可能使这些细胞成为未来治疗应用的良好潜在来源。
Several types of nonhematopoietic stem cells, including bone marrow mesenchymal stem cells (BMMSCs) and embryonic stem cells, have been shown to have immunosuppressive properties. We show that human placenta-derived multipotent cells (PDMCs), which are isolated from a source without ethical concern and harbor multilineage differentiation potential, have strong immunosuppressive properties. PDMCs suppress both mitogen-induced and allogeneic lymphocyte proliferation in both CD4 and CD8 populations. The immunosuppression seen with PDMCs was significantly stronger than that with BMMSCs. Both PDMCs and BMMSCs express indoleamine 2,3-dioxygenase, but only PDMCs are positive for intracellular human leukocyte antigen-G (HLA). Mechanistically, suppression of lymphocyte reactivity by PDMCs is not due to cell death but to decreased cell proliferation and increased numbers of regulatory T cells. Addition of neutralizing antibodies to interleukin-10 and transforming growth factor (TGF)-beta partially restored lymphocyte proliferation. Unlike BMMSCs, PDMCs treated with interferon-gamma for 3 days only very minimally upregulated HLA-DR. On the contrary, PD-L1, a cell surface marker that plays an inhibitory role in T-cell activation, was upregulated and TGF-beta expression was seen. The immunosuppressive properties of PDMCs, along with their multilineage differentiation potential, ease of accessibility, and abundant cell numbers, may render these cells as good potential sources for future therapeutic applications.