Kruse Vanessa, Hamann Carina, Monecke Sebastian, Cyganek Lukas, Elsner Leslie, Hübscher Daniela, Walter Lutz, Streckfuss-Bömeke Katrin, Guan Kaomei, Dressel Ralf
Department of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, Germany.
Department of Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany; DZHK (German Center for Cardiovascular Research), Partner site Göttingen, Germany.
PLoS One. 2015 May 7;10(5):e0125544. doi: 10.1371/journal.pone.0125544. eCollection 2015.
Human induced pluripotent stem cells (hiPSCs) could be used to generate autologous cells for therapeutic purposes, which are expected to be tolerated by the recipient. However, iPSC-derived grafts are at risk of giving rise to teratomas in the host, if residuals of tumorigenic cells are not rejected by the recipient. We have analyzed the susceptibility of hiPSC lines to allogeneic and autologous natural killer (NK) cells. IL-2-activated, in contrast to resting NK cells killed hiPSC lines efficiently (P = 1.69 x 10(-39)). Notably, the specific lysis of the individual hiPSC lines by IL-2-activated NK cells was significantly different (P = 1.72 x 10(-6)) and ranged between 46 % and 64 % in 51Cr-release assays when compared to K562 cells. The hiPSC lines were killed by both allogeneic and autologous NK cells although autologous NK cells were less efficient (P=8.63 x 10(-6)). Killing was partly dependent on the activating NK receptor DNAM-1 (P = 8.22 x 10(-7)). The DNAM-1 ligands CD112 and CD155 as well as the NKG2D ligands MICA and MICB were expressed on the hiPSC lines. Low amounts of human leukocyte antigen (HLA) class I proteins, which serve as ligands for inhibitory and activating NK receptors were also detected. Thus, the susceptibility to NK cell killing appears to constitute a common feature of hiPSCs. Therefore, NK cells might reduce the risk of teratoma formation even after autologous transplantations of pluripotent stem cell-derived grafts that contain traces of pluripotent cells.
人诱导多能干细胞（hiPSC）可用于生成自体细胞用于治疗目的，预计受体可耐受这些细胞。然而，如果致瘤细胞残余物未被受体排斥，iPSC衍生的移植物在宿主体内有形成畸胎瘤的风险。我们分析了hiPSC系对同种异体和自体自然杀伤（NK）细胞的敏感性。与静息NK细胞相比，IL-2激活的NK细胞能有效杀伤hiPSC系（P = 1.69×10⁻³⁹）。值得注意的是，IL-2激活的NK细胞对各个hiPSC系的特异性杀伤作用存在显著差异（P = 1.72×10⁻⁶），在⁵¹Cr释放试验中，与K562细胞相比，杀伤率在46%至64%之间。hiPSC系既能被同种异体NK细胞也能被自体NK细胞杀伤，尽管自体NK细胞的杀伤效率较低（P = 8.63×10⁻⁶）。杀伤作用部分依赖于激活型NK受体DNAM-1（P = 8.22×10⁻⁷）。hiPSC系表达DNAM-1配体CD112和CD155以及NKG2D配体MICA和MICB。还检测到少量作为抑制性和激活性NK受体配体的人类白细胞抗原（HLA）I类蛋白。因此，对NK细胞杀伤的敏感性似乎是hiPSC的一个共同特征。所以，即使在含有微量多能细胞的多能干细胞衍生移植物自体移植后，NK细胞也可能降低畸胎瘤形成的风险。
