Cloned, CD117 selected human amniotic fluid stem cells are capable of modulating the immune response.
Cloned, CD117 selected human amniotic fluid stem cells are capable of modulating the immune response.
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DOI：
10.1371/journal.pone.0026535
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Bishop CE
中科院分区：
文献类型：
--
作者：
Moorefield EC;McKee EE;Solchaga L;Orlando G;Yoo JJ;Walker S;Furth ME;Bishop CE
羊水干细胞 (AFS) 具有广泛的多能性，可以在培养物中广泛扩增，不具有致瘤性，并且可以轻松冷冻保存用于细胞库。间充质干细胞（MSC）表现出免疫调节活性，并分泌多种细胞因子和趋化因子，抑制炎症反应，阻断混合淋巴细胞反应（MLR）和其他免疫反应，并已被证明可以治疗移植物抗宿主病等疾病。 AFS 细胞在许多方面类似于 MSC，包括表面标记表达和分化潜力。因此，我们假设 AFS 细胞可能表现出类似的免疫调节能力。我们提供的数据证明与 AFS 细胞直接接触会抑制淋巴细胞活化。此外，我们还发现，用全血单核细胞或 IL-1β（一种单核细胞释放的细胞因子，对介导炎症反应至关重要）的 AFS 细胞衍生的无细胞上清液也抑制淋巴细胞活化。通过蛋白质阵列对 AFS 无细胞上清液进行进一步研究，揭示了与 MSC 共同分泌的多种因子，这些因子已知参与免疫调节，包括生长相关癌基因 (GRO) 和单核细胞趋化蛋白 (MCP) 家族成员以及白细胞介素 6 (IL-6)。与 BM-MSC 相比，PBMC 激活的 AFS 细胞释放了几种额外的细胞因子，包括巨噬细胞炎症蛋白 3α (MIP-3α)、MIP-1α 和激活素。与 BM-MSC 相比，AFS 细胞响应 IL-1β 激活也释放了更高水平的 MCP-1 和更低水平的 MCP-2。这表明可能存在一些 AFS 特异性抑制淋巴细胞活化的机制。我们的结果表明，AFS 细胞能够在体外抑制炎症反应，并且可溶性因子是淋巴细胞和 AFS 细胞之间通讯的重要组成部分。其广泛的自我更新能力、储存的可能性以及无致瘤性可能使 AFS 细胞成为用于各种免疫疗法的稳定、特征良好的“现成”免疫调节细胞的优质来源。
Amniotic fluid stem (AFS) cells are broadly multipotent, can be expanded extensively in culture, are not tumorigenic and can be readily cryopreserved for cell banking. Mesenchymal stem cells (MSC) show immunomodulatory activity and secrete a wide spectrum of cytokines and chemokines that suppress inflammatory responses, block mixed lymphocyte reactions (MLR) and other immune reactions, and have proven therapeutic against conditions such as graft-versus-host disease. AFS cells resemble MSCs in many respects including surface marker expression and differentiation potential. We therefore hypothesized that AFS cells may exhibit similar immunomodulatory capabilities. We present data to demonstrate that direct contact with AFS cells inhibits lymphocyte activation. In addition, we show that cell-free supernatants derived from AFS cells primed with total blood monocytes or IL-1β, a cytokine released by monocytes and essential in mediation of the inflammatory response, also inhibited lymphocyte activation. Further investigation of AFS cell-free supernatants by protein array revealed secretion of multiple factors in common with MSCs that are known to be involved in immune regulation including growth related oncogene (GRO) and monocyte chemotactic protein (MCP) family members as well as interleukin-6 (IL-6). AFS cells activated by PBMCs released several additional cytokines as compared to BM-MSCs, including macrophage inflammatory protein-3α (MIP-3α), MIP-1α and Activin. AFS cells also released higher levels of MCP-1 and lower levels of MCP-2 compared to BM-MSCs in response to IL-1β activation. This suggests that there may be some AFS-specific mechanisms of inhibition of lymphocyte activation. Our results indicate that AFS cells are able to suppress inflammatory responses in vitro and that soluble factors are an essential component in the communication between lymphocytes and AFS cells. Their extensive self-renewal capacity, possibility for banking and absence of tumorigenicity may make AFS cells a superior source of stable, well characterized “off the shelf” immunomodulatory cells for a variety of immunotherapies.
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