MHC matching improves engraftment of iPSC-derived neurons in non-human primates.
MHC matching improves engraftment of iPSC-derived neurons in non-human primates.
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MHC匹配改善了非人类灵长类动物中IPSC衍生的神经元的植入。
DOI：
10.1038/s41467-017-00926-5
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发表时间：
2017-08-30
影响因子：
16.6
通讯作者：
Takahashi J
中科院分区：
文献类型：
--
作者：
Morizane A;Kikuchi T;Hayashi T;Mizuma H;Takara S;Doi H;Mawatari A;Glasser MF;Shiina T;Ishigaki H;Itoh Y;Okita K;Yamasaki E;Doi D;Onoe H;Ogasawara K;Yamanaka S;Takahashi J
人类白细胞抗原（HLA）纯合子诱导的多能干细胞（iPSCs）被认为是HLA匹配细胞移植的未来临床策略，以减少免疫移植排斥反应。在这里，我们展示了主要组织相容性复合体（MHC）匹配的同种异体神经细胞移植到大脑中的效果，这被认为是免疫反应较差的组织，使用来自MHC纯合食蟹猕猴的iPSCs。正电子发射断层成像显示神经炎症与mhc错配移植细胞的免疫反应相关。免疫组织学分析显示mhc匹配通过抑制小胶质细胞（Iba-1+）和淋巴细胞（CD45+）在移植物中的积累来降低免疫反应。因此，mhc匹配增加了移植多巴胺神经元（酪氨酸羟化酶：TH+）的存活率。免疫抑制剂他克莫司的效果也在同一实验环境中得到证实。我们的结果证明了mhc匹配神经细胞移植到大脑的基本原理及其在临床环境中的可行性。主要组织相容性复合体（MHC）匹配提高器官移植后移植物存活率。在这里，作者表明，在猕猴中，mhc匹配的ipsc来源的神经元在大脑中提供了更好的植入，具有较低的免疫反应和较高的移植神经元存活率。
The banking of human leukocyte antigen (HLA)-homozygous-induced pluripotent stem cells (iPSCs) is considered a future clinical strategy for HLA-matched cell transplantation to reduce immunological graft rejection. Here we show the efficacy of major histocompatibility complex (MHC)-matched allogeneic neural cell grafting in the brain, which is considered a less immune-responsive tissue, using iPSCs derived from an MHC homozygous cynomolgus macaque. Positron emission tomography imaging reveals neuroinflammation associated with an immune response against MHC-mismatched grafted cells. Immunohistological analyses reveal that MHC-matching reduces the immune response by suppressing the accumulation of microglia (Iba-1+) and lymphocytes (CD45+) into the grafts. Consequently, MHC-matching increases the survival of grafted dopamine neurons (tyrosine hydroxylase: TH+). The effect of an immunosuppressant, Tacrolimus, is also confirmed in the same experimental setting. Our results demonstrate the rationale for MHC-matching in neural cell grafting to the brain and its feasibility in a clinical setting. Major histocompatibility complex (MHC) matching improves graft survival rates after organ transplantation. Here the authors show that in macaques, MHC-matched iPSC-derived neurons provide better engraftment in the brain, with a lower immune response and higher survival of the transplanted neurons.
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影响因子：
5.9
作者：
Doi, Daisuke;Samata, Bumpei;Katsukawa, Mitsuko;Kikuchi, Tetsuhiro;Morizane, Asuka;Ono, Yuichi;Sekiguchi, Kiyotoshi;Nakagawa, Masato;Parmar, Malin;Takahashi, Jun
通讯作者：
Takahashi, Jun
影响因子：
8.8
作者：
Emborg ME;Liu Y;Xi J;Zhang X;Yin Y;Lu J;Joers V;Swanson C;Holden JE;Zhang SC
通讯作者：
Zhang SC
影响因子：
5.7
作者：
Gunn, RN;Lammertsma, AA;Cunningham, VJ
通讯作者：
Cunningham, VJ
影响因子：
3.2
作者：
Kita, Yuki F.;Hosomichi, Kazuyoshi;Shiina, Takashi
通讯作者：
Shiina, Takashi
影响因子：
5.7
作者：
Dale, AM;Fischl, B;Sereno, MI
通讯作者：
Sereno, MI