The immunogenicity and immunomodulatory function of osteogenic cells differentiated from mesenchymal stem cells
The immunogenicity and immunomodulatory function of osteogenic cells differentiated from mesenchymal stem cells
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DOI：
10.4049/jimmunol.176.5.2864
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发表时间：
2006-03-01
影响因子：
4.4
通讯作者：
Cao, Tong
中科院分区：
文献类型：
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作者：
Liu, Hua;Kemeny, David Michael;Cao, Tong
据报道，多能间充质干细胞（MSC）是免疫豁免的以及免疫抑制的。因此，它们是用于同种异体移植以诱导患病组织和器官再生的理想候选物。然而，尚不清楚MSC在分化为移植部位的局部细胞类型后是否会保留其免疫豁免和免疫调节特性。本研究试图用一种新的新西兰白色兔成骨模型来研究这个问题。结果表明，从MSC（DOC）在体外分化成骨细胞不表达MHC II类分子，不能诱导同种异体淋巴细胞增殖混合淋巴细胞培养或产生CTL，抑制正在进行的淋巴细胞增殖，并分泌抗炎细胞因子（IL-10和TGF-β）。DOC分泌IL-10的能力显著高于MSC，而MSC分泌TGF-β的能力与DOC无显著差异。然而，IFN-γ治疗后，尽管MSC的产量增加，DOC的TGF-β分泌显着下降。局部DOC植入后四周，尽管MHC II类表达，第二组同种异体皮肤排斥反应显示出与第一组同种异体皮肤排斥反应相似的存活率，DOC似乎起成骨细胞的作用。总之，DOC在体外保留了其免疫豁免和免疫调节特性，但后者在移植后丧失。
Multipotent mesenchymal stem cells (MSC) are reported to be immunoprivileged as well as immunosuppressive. Hence, they are ideal candidates for allogeneic transplantation to induce regeneration of diseased tissues and organs. However, it is not known whether MSC would retain their immunoprivileged and immunomodulatory properties after differentiating into the local cell types of the transplantation site. This study sought to investigate this question with a novel New Zealand White rabbit osteogenesis model. Results showed that osteogenic cells differentiated from MSC (DOC) in vitro did not express the MHC class II molecule, were incapable of inducing allogeneic lymphocyte proliferation in mixed lymphocyte culture or generating CTL, were inhibitory in ongoing lymphocyte proliferation, and secreted anti-inflammatory cytokines (IL-10 and TGF-beta). There was a significantly higher secretion of IL-10 by DOC than that by MSC, while there was no significant difference between the TGF-beta secretion of MSC and DOC in vitro. However, after IFN-gamma treatment, TGF-beta secretion by DOC significantly decreased despite the increased production by MSC. Four weeks after local DOC implantation, despite MHC class II expression, second-set allogeneic skin rejection showed similar survival to first-set allogeneic skin rejection and DOC appeared to function as osteoblasts. In conclusion, DOC retained their immunoprivileged and immunomodulatory properties in vitro, but the latter was lost following transplantation.