Immunosuppressive effect of bone marrow-derived mesenchymal stem cells in inflammatory microenvironment favours the growth of B16 melanoma cells.
Immunosuppressive effect of bone marrow-derived mesenchymal stem cells in inflammatory microenvironment favours the growth of B16 melanoma cells.
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炎症微环境中骨髓间充质干细胞的免疫抑制作用有利于B16黑色素瘤细胞的生长
DOI：
10.1111/j.1582-4934.2010.01215.x
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发表时间：
2011-11
影响因子：
5.3
通讯作者：
Wei L
中科院分区：
文献类型：
--
作者：
Han Z;Tian Z;Lv G;Zhang L;Jiang G;Sun K;Wang C;Bu X;Li R;Shi Y;Wu M;Wei L
人们正在研究间充质干细胞 (MSC) 在再生医学、组织工程和肿瘤治疗中的潜在临床用途。然而，除非更好地了解 MSC 对体内肿瘤生长的免疫抑制作用，否则 MSC 在肿瘤治疗中的治疗应用仍然有限。在这项研究中，我们研究了间充质干细胞有利于肿瘤逃避炎症微环境中的免疫监视的机制。我们首先比较了骨髓间充质干细胞在体内（无论是否预孵育）与炎症细胞因子干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α对B16黑色素瘤细胞生长的促进能力。我们发现，与对照组相比，与预孵育 IFN-γ 和 TNF-α 的 MSC 共同注射时，B16 黑色素瘤细胞的发育更快。此外，当 B16 黑色素瘤细胞与预孵育 IFN-γ 和 TNF-α 的 MSC 共同注射时，同种异体受者的肿瘤发病率明显增加。然后我们证明 MSC 的免疫抑制功能是由 IFN-γ 和 TNF-α 引起的。这些细胞因子组合激发 MSC 表达诱导型一氧化氮合酶 (iNOS)。用炎性细胞因子处理的MSC在体内对B16黑色素瘤细胞的脉冲作用可以被iNOS的抑制剂或短干扰RNA逆转。我们的研究结果表明，肿瘤炎症微环境中的间充质干细胞可能会引发免疫抑制功能，从而帮助肿瘤逃避免疫监视。
Mesenchymal stem cells (MSCs) are studied for their potential clinical use in regenerative medicine, tissue engineering and tumour therapy. However, the therapeutic application of MSCs in tumour therapy still remains limited unless the immunosuppressive role of MSCs for tumour growth in vivo is better understood. In this study, we investigated the mechanism of MSCs favouring tumour escape from immunologic surveillance in inflammatory microenvironment. We first compared the promotive capacity of bone marrow‐derived MSCs on B16 melanoma cells growth in vivo, pre‐incubated or not with the inflammatory cytokines interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α. We showed that the development of B16 melanoma cells is faster when co‐injected with MSCs pre‐incubated with IFN‐γ and TNF‐α compared with control groups. Moreover, tumour incidence increases obviously in allogeneic recipients when B16 melanoma cells were co‐injected with MSCs pre‐incubated with IFN‐γ and TNF‐α. We then demonstrated that the immunosuppressive function of MSCs was elicited by IFN‐γ and TNF‐α. These cytokine combinations provoke the expression of inducible nitric oxide synthase (iNOS) by MSCs. The impulsive effect of MSCs treated with inflammatory cytokines on B16 melanoma cells in vivo can be reversed by inhibitor or short interfering RNA of iNOS. Our results suggest that the MSCs in tumour inflammatory microenvironment may be elicited of immunosuppressive function, which will help tumour to escape from the immunity surveillance.
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影响因子：
20.3
作者：
Sato, Kazuya;Ozaki, Katsutoshi;Ozawa, Keiya
通讯作者：
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影响因子：
11.2
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20.3
作者：
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作者：
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作者：
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