HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells
HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells
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DOI：
10.1016/s0301-472x(03)00110-3
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发表时间：
2003-10-01
影响因子：
2.6
通讯作者：
Ringdén, O
中科院分区：
文献类型：
--
作者：
Le Blanc, K;Tammik, C;Ringdén, O
Objective.间充质干细胞（MSC）不引起同种异体反应性淋巴细胞反应，由于免疫调节。我们研究了MSC分化后的免疫学特性，沿着三个谱系：骨，软骨，脂肪。流式细胞术显示，未分化的MSC表达HLA I类，但不表达HLA II类，虽然HLA II类存在于细胞内，通过Western blot检测。添加干扰素γ（IFN-γ）48小时诱导大于90%的细胞表达HLA II类。同种异体辐射MSC作为刺激物没有诱导淋巴细胞反应。使用MSC预处理的结果相似。IFN-γ细胞在培养基中生长以诱导分化为骨、软骨或脂肪6或12天后，HLA I类的表达增加，但在细胞表面上未检测到II类。暴露于IFN-γ 48小时后上调细胞表面上的HLA II类的能力在细胞在分化培养基中培养6或12天后明显减弱，只有10%的细胞表达HLA II类。使用MSC在成骨、成软骨或成脂培养基中生长作为刺激细胞，没有看到淋巴细胞同种异体反应性，即使分化的MSC已经用IFN-γ预处理。MSC抑制混合淋巴细胞培养，特别是在成骨分化后。IFN-γ进一步增强了这种抑制作用。未分化和分化的MSC不引起同种异体反应性淋巴细胞增殖反应和调节免疫反应。研究结果支持MSC可以在HLA不相容的个体之间移植。(C)2003年国际实验血液学学会。爱思唯尔公司出版
Objective. Mesenchymal stem cells (MSC) do not elicit alloreactive lymphocyte responses due to immune modulations. We investigated the immunologic properties of MSC after differentiation along three lineages: bone, cartilage, and adipose.Methods and Results. Flow cytometry showed that undifferentiated MSC express HLA class I but not class II, although HLA class II was present intracellularly as detected by Western blot. Addition of interferon gamma (IFN-gamma) for 48 hours induced greater than 90% of cells to express HLA class II. No lymphocyte response was induced by allogeneic irradiated MSC as stimulators. Results were similar using MSC pretreated. with IFN-gamma. After growth of cells in medium to induce differentiation to bone, cartilage, or adipose for 6 or 12 days, the expression of HLA class I increased but no class II was detected on the cell surface. The ability to upregulate HLA class II on the cell surface after exposure to IFN-gamma for 48 hours was clearly diminished after the cells had been cultured in differentiation medium for 6 or 12 days, with only 10% of cells expressing HLA class II. Using MSC grown in osteogenic, chondrogenic, or adipogenic medium as stimulator cells, no lymphocyte alloreactivity was seen, even if differentiated MSC had been pretreated with IFN-gamma. MSC inhibit mixed lymphocyte cultures, particularly after osteogenic differentiation. This suppression was further enhanced by IFN-gamma.Conclusion. Undifferentiated and differentiated MSC do not elicit alloreactive lymphocyte proliferative responses and modulate immune responses. The findings support that MSC can be transplantable between HLA-incompatible individuals. (C) 2003 International Society for Experimental Hematology. Published by Elsevier Inc.