Human mesenchymal stem cells derived from induced pluripotent stem cells down-regulate NK-cell cytolytic machinery
Human mesenchymal stem cells derived from induced pluripotent stem cells down-regulate NK-cell cytolytic machinery
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DOI：
10.1182/blood-2010-12-325324
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发表时间：
2011-09-22
期刊：
影响因子：
20.3
通讯作者：
Bennaceur-Griscelli, Annelise
中科院分区：
文献类型：
--
作者：
Giuliani, Massimo;Oudrhiri, Noufissa;Bennaceur-Griscelli, Annelise
免疫抑制生物治疗的一个主要问题是使用具有调节能力的间充质干细胞（MSC）。然而，目前使用的骨髓源性间充质干细胞（BM-MSCs）是短命的，不能保证长期持久的免疫调节功能，在体外和体内。因此，我们已经从人诱导多能干细胞（IPS-MSC）细胞中产生了MSC，这些细胞与胚胎干细胞（ES-MSC）具有相似的特性。在此，我们比较了ES/IPS-MSCs与BM-MSCs的免疫调节特性，并首次表明，IPS衍生的MSCs以与ES-MSCs相似的方式显示出显著的NK细胞增殖抑制和细胞溶解功能。两种MSC均以与BM-MSC相同的方式通过下调不同活化标志物和ERK 1/2信号传导的表达来破坏NK细胞的细胞溶解机制，导致与靶细胞形成免疫突触的损伤，并因此导致细胞毒性颗粒的分泌。此外，它们比成人BM-MSC对预活化的NK细胞更具抗性。IPS-MSCs可能是一种有吸引力的免疫调节细胞的替代来源，它们削弱NK细胞细胞毒性的能力构成了防止同种异体移植排斥反应的复杂机制。（血。2011;118（12）：3254-3262）
A major issue in immunosuppressive biotherapy is the use of mesenchymal stem cells (MSCs) that harbor regulatory capacity. However, currently used bone marrow-derived MSCs (BM-MSCs) are short-lived and cannot assure long lasting immunoregulatory function both in vitro and in vivo. Consequently, we have generated MSCs from human induced pluripotent stem (IPS-MSCs) cells that share similar properties with embryonic stem cells (ES-MSCs). Herein, we compared the immunoregulatory properties of ES/IPS-MSCs with those of BM-MSCs and showed, for the first time, that IPS-derived MSCs display remarkable inhibition of NK-cell proliferation and cytolytic function in a similar way to ES-MSCs. Both MSCs disrupt NK-cell cytolytic machinery in the same fashion that BM-MSCs, by down-regulating the expression of different activation markers and ERK1/2 signaling, leading to an impairment to form immunologic synapses with target cells and, therefore, secretion of cytotoxic granules. In addition, they are more resistant than adult BM-MSCs to preactivated NK cells. IPS-MSCs could represent an attractive alternative source of immunoregulatory cells, and their capacity to impair NK-cell cytotoxicity constitutes a complex mechanism to prevent allograft rejection. (Blood. 2011;118(12):3254-3262)