Direct comparison of autologous and allogeneic transplantation of iPSC-derived neural cells in the brain of a non-human primate.
Direct comparison of autologous and allogeneic transplantation of iPSC-derived neural cells in the brain of a non-human primate.
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DOI：
10.1016/j.stemcr.2013.08.007
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发表时间：
2013
影响因子：
5.9
通讯作者：
Takahashi, Jun
中科院分区：
文献类型：
--
作者：
Morizane, Asuka;Doi, Daisuke;Kikuchi, Tetsuhiro;Okita, Keisuke;Hotta, Akitsu;Kawasaki, Toshiyuki;Hayashi, Takuya;Onoe, Hirotaka;Shiina, Takashi;Yamanaka, Shinya;Takahashi, Jun
诱导多能干细胞 (iPSC) 提供了使用源自患者自身细胞的细胞进行自体移植的潜力。然而，iPSC或其衍生物的免疫原性一直存在争议，迄今为止还没有对人类或非人灵长类动物大脑中的自体和同种异体移植进行直接比较。在这里，我们使用非人类灵长类动物，发现 iPSC 衍生神经元的自体移植仅在大脑中引起最小的免疫反应。相比之下，同种异体移植物引起获得性免疫反应，激活小胶质细胞（IBA-1+/MHC II+）和白细胞浸润（CD45+/CD3+）。因此，更多数量的多巴胺能神经元在自体移植物中存活。我们的结果表明，与同种异体移植相比，iPSC 衍生神经细胞的自体移植有利于最大限度地减少大脑中的免疫反应。 iPSC 衍生的自体移植物仅在灵长类动物大脑中引起最小的免疫反应 即使在免疫豁免部位，自体移植物也比同种异体移植物具有优势 即使在没有免疫抑制的同种异体移植物中，多巴胺神经元也能存活 iPSC 衍生的神经元的自体移植仅在大脑中引起最小的免疫反应。相比之下，同种异体移植物引起获得性免疫反应，激活小胶质细胞（IBA-1+/MHC II+）和白细胞浸润（CD45+/CD3+）。与同种异体移植相比，自体移植有利于最大限度地减少免疫反应。
Induced pluripotent stem cells (iPSCs) provide the potential for autologous transplantation using cells derived from a patient’s own cells. However, the immunogenicity of iPSCs or their derivatives has been a matter of controversy, and up to now there has been no direct comparison of autologous and allogeneic transplantation in the brains of humans or nonhuman primates. Here, using nonhuman primates, we found that the autologous transplantation of iPSC-derived neurons elicited only a minimal immune response in the brain. In contrast, the allografts caused an acquired immune response with the activation of microglia (IBA-1+/MHC class II+) and the infiltration of leukocytes (CD45+/CD3+). Consequently, a higher number of dopaminergic neurons survived in the autografts. Our results suggest that the autologous transplantation of iPSC-derived neural cells is advantageous for minimizing the immune response in the brain compared with allogeneic grafts. iPSC-derived autografts cause only a minimal immune response in the primate brain Autografts have advantages over allografts even at an immune-privileged site Dopamine neurons survive even in allografts without immunosuppression The autologous transplantation of iPSC-derived neurons elicited only a minimal immune response in the brain. In contrast, the allografts caused an acquired immune response with the activation of microglia (IBA-1+/MHC class II+) and the infiltration of leukocytes (CD45+/CD3+). Autologous transplantation is advantageous for minimizing the immune response compared with allogeneic grafts.
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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：
5.2
作者：
Deleidi, Michela;Hargus, Gunnar;Hallett, Penelope;Osborn, Teresia;Isacson, Ole
通讯作者：
Isacson, Ole
DOI：
10.1016/j.bbadis.2010.07.008
发表时间：
2011-02
影响因子：
6.2
作者：
Chastain, Emily M. L.;Duncan, D'Anne S.;Rodgers, Jane M.;Miller, Stephen D.
通讯作者：
Miller, Stephen D.
影响因子：
11.2
作者：
Olanow, CW;Goetz, CG;Freeman, TB
通讯作者：
Freeman, TB
影响因子：
2.5
作者：
HUDSON, JL;HOFFMAN, A;MOORHEAD, JW
通讯作者：
MOORHEAD, JW