Brief Report: Immune Microenvironment Determines the Immunogenicity of Induced Pluripotent Stem Cell Derivatives
Brief Report: Immune Microenvironment Determines the Immunogenicity of Induced Pluripotent Stem Cell Derivatives
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免疫微环境决定 iPSC 衍生物的免疫原性
DOI：
10.1002/stem.2227
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发表时间：
2016-02-01
期刊：
影响因子：
5.2
通讯作者：
Xu, Yang
中科院分区：
文献类型：
--
作者：
Todorova, Dilyana;Kim, Jinchul;Xu, Yang
诱导多能干细胞（iPSC）的突破提高了患者特异性iPSC可以为细胞治疗提供自体细胞而无需担心免疫排斥的可能性。然而，iPSC衍生细胞的免疫原性仍然存在争议。使用同基因C57 BL/6（B6）小鼠移植模型，若干研究表明，当皮下移植到B6小鼠中时，B6 iPSC衍生的细胞表现出一定水平的免疫原性。相比之下，最近的一项研究得出结论，当移植到B6小鼠的肾包膜下时，B6 iPSC衍生细胞的各种谱系没有表现出免疫原性。为了解决有关iPSC生物学这一关键问题的争议，我们使用相同的B6移植模型来证明对抗原的免疫应答取决于移植部位的免疫环境。表达免疫原性抗原的B6胚胎干细胞（ESC）以及B6 iPSC及其终末分化的细胞在肾包膜下存活，但当皮下或肌内移植时被免疫排斥。成熟B6树突状细胞在肾被膜下的共移植导致B6 iPSC衍生的移植物的免疫排斥，但不导致B6 ESC衍生的移植物的免疫排斥，这表明在肾被膜下缺乏对iPSC衍生的移植物的可检测的免疫应答是由于缺乏功能性抗原呈递细胞。
The breakthrough of induced pluripotent stem cells (iPSCs) has raised the possibility that patient-specific iPSCs can provide autologous cells for cell therapy without the concern for immune rejection. However, the immunogenicity of iPSC-derived cells remains controversial. Using syngeneic C57BL/6 (B6) mouse transplantation model, several studies indicate that B6 iPSC-derived cells exhibit some levels of immunogenicity when transplanted into B6 mice subcutaneously. In contrast, one recent study has concluded that various lineages of B6 iPSC-derived cells exhibit no immunogenicity when transplanted under the kidney capsule of B6 mice. To resolve the controversy concerning this critical issue of iPSC biology, we used the same B6 transplantation model to demonstrate that the immune response toward antigens is dependent on the immune environment of the transplantation site. Immunogenic antigen-expressing B6 embryonic stem cells (ESCs) as well as B6 iPSCs and their terminally differentiated cells survived under the kidney capsule but are immune rejected when transplanted subcutaneously or intramuscularly. The cotransplantation of mature B6 dendritic cells under the kidney capsule leads to immune rejection of B6 iPSC-derived grafts but not B6 ESC-derived grafts, indicating that the lack of detectable immune response to iPSC-derived grafts under the kidney capsule is due to the lack of functional antigen presenting cells.