Pluripotent stem cells are highly susceptible targets for syngeneic, allogeneic, and xenogeneic natural killer cells
Pluripotent stem cells are highly susceptible targets for syngeneic, allogeneic, and xenogeneic natural killer cells
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DOI：
10.1096/fj.09-134957
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发表时间：
2010-07-01
期刊：
影响因子：
4.8
通讯作者：
Engel, Wolfgang
中科院分区：
文献类型：
--
作者：
Dressel, Ralf;Nolte, Jessica;Engel, Wolfgang
多能成体生殖系干细胞（maGSC）和诱导多能干细胞（iPSC）可用于产生用于治疗目的的自体细胞，预期其可被受体耐受。然而，免疫系统对这些细胞的影响尚未研究。我们比较了maGSC系与胚胎干细胞（ESC）系、iPSC和F9畸胎瘤细胞对IL-2激活的自然杀伤（NK）细胞的易感性。在铬释放试验中，与作为高度敏感参考细胞的YAC-1细胞相比，同基因、同种异体和异种杀伤细胞对多能细胞系的杀伤范围在48%至265%之间。除2个maGSC系外，它们表达属于RAE-1家族的活化NK受体NKG 2D的配体，并且杀伤可被可溶性NKG 2D抑制，证明了这些分子的功能作用。此外，活化受体DNAM-1的配体频繁表达。对NK细胞的易感性可能构成多能细胞的共同特征。它可能导致移植后的排斥反应，正如体内NK细胞活化后畸胎瘤生长减少所表明的那样，但它也可能提供一种在移植分化细胞之前耗尽污染多能细胞的策略。德雷塞尔河Nolte，J.，埃尔斯纳湖，Novota，P.，Guan，K.，Streckfuss-Bomeke，K.，Hasenfuss，G.，耶尼施河，Engel，W.多能干细胞是同基因、同种异体和异种自然杀伤细胞高度敏感的靶细胞。FASEB J.24，2164-2177（2010）。www.fasebj.org
Multipotent adult germ-line stem cells (maGSCs) and induced pluripotent stem cells (iPSCs) could be used to generate autologous cells for therapeutic purposes, which are expected to be tolerated by the recipient. However, effects of the immune system on these cells have not been investigated. We have compared the susceptibility of maGSC lines to IL-2-activated natural killer (NK) cells with embryonic stem cell (ESC) lines, iPSCs, and F9 teratocarcinoma cells. The killing of pluripotent cell lines by syngeneic, allogeneic, and xenogeneic killer cells ranged between 48 and 265% in chromium release assays when compared to YAC-1 cells, which served as highly susceptible reference cells. With the exception of 2 maGSC lines, they expressed ligands for the activating NK receptor NKG2D that belong to the RAE-1 family, and killing could be inhibited by soluble NKG2D, demonstrating a functional role of these molecules. Furthermore, ligands of the activating receptor DNAM-1 were frequently expressed. The susceptibility to NK cells might constitute a common feature of pluripotent cells. It could result in rejection after transplantation, as suggested by a reduced teratoma growth after NK cell activation in vivo, but it might also offer a strategy to deplete contaminating pluripotent cells before grafting of differentiated cells.-Dressel, R., Nolte, J., Elsner, L., Novota, P., Guan, K., Streckfuss-Bomeke, K., Hasenfuss, G., Jaenisch, R., Engel, W. Pluripotent stem cells are highly susceptible targets for syngeneic, allogeneic, and xenogeneic natural killer cells. FASEB J. 24, 2164-2177 (2010). www.fasebj.org