Successful Transplantation of Retinal Pigment Epithelial Cells from MHC Homozygote iPSCs in MHC-Matched Models.

Successful Transplantation of Retinal Pigment Epithelial Cells from MHC Homozygote iPSCs in MHC-Matched Models.
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DOI:
10.1016/j.stemcr.2016.08.010
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发表时间:
2016-10-11
期刊:
影响因子:
5.9
通讯作者:
Takahashi, Masayo
Takahashi, Masayo
中科院分区:
医学1区
文献类型:
--
作者:
Sugita, Sunao;Iwasaki, Yuko;Makabe, Kenichi;Kamao, Hiroyuki;Mandai, Michiko;Shiina, Takashi;Ogasawara, Kazumasa;Hirami, Yasuhiko;Kurimoto, Yasuo;Takahashi, Masayo

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主要组织相容性复合体(MHC)配型是否是异基因干细胞移植的解决方案一直存在争议。在本研究中,我们建立了视网膜色素上皮(RPE)细胞诱导多能干细胞(iPSC)在MHC纯合子供体。我们在没有免疫抑制的MHC匹配的动物模型的iPSC衍生的RPE同种异体移植物中没有观察到排斥迹象,而在MHC不匹配的模型中,移植物周围存在免疫攻击和视网膜组织损伤。在MHC不匹配的同种异体移植物的免疫组织化学检查中,移植的RPE片/细胞位于视网膜下腔,但RPE表现出炎症和肥大变化,并且许多炎性细胞,例如,Iba 1+细胞、MHC II类+细胞和CD 3 + T细胞侵入移植物区域。相反,如果使用MHC匹配的同种异体移植物,这些炎性细胞很少浸润移植视网膜周围的区域。因此,来自MHC纯合供体的细胞可用于治疗组织相容性受体的视网膜疾病。我们在MHC纯合子动物中建立了来自iPSC的RPE细胞MHC错配移植引起了iPS-RPE同种异体移植物的免疫攻击MHC匹配移植似乎可以防止同种异体移植物的攻击T细胞对同种异体iPS-RPE有反应,但对MHC纯合子RPE没有反应在这篇文章中,Takahashi及其同事展示了同种异体免疫反应,如免疫排斥,体内炎症细胞对iPSC衍生的视网膜色素上皮(RPE)细胞的作用。然而,当移植从MHC纯合供体建立的iPS-RPE细胞时,不发生免疫反应。
There is an ongoing controversy as to whether major histocompatibility complex (MHC) matching is a solution for allogeneic stem cell transplantation. In the present study, we established retinal pigment epithelial (RPE) cells from induced pluripotent stem cells (iPSCs) in MHC homozygote donors. We observed no rejection signs in iPSC-derived RPE allografts of MHC-matched animal models without immunosuppression, whereas there were immune attacks around the graft and retinal tissue damage in MHC-mismatched models. In an immunohistochemical examination of MHC-mismatched allografts, the transplanted RPE sheets/cells were located in the subretinal space, but the RPE exhibited inflammatory and hypertrophic changes, and many inflammatory cells, e.g., Iba1+ cells, MHC class II+ cells, and CD3+ T cells, invaded the graft area. Conversely, these inflammatory cells poorly infiltrated the area around the transplanted retina if MHC-matched allografts were used. Thus, cells derived from MHC homozygous donors could be used to treat retinal diseases in histocompatible recipients. We established RPE cells from iPSCs in MHC homozygote animals MHC-mismatching transplantation caused immune attacks of iPS-RPE allografts MHC-matching transplantation appeared to prevent the attacks of the allografts T cells responded to allogeneic iPS-RPE, but failed to respond to MHC homozygote RPE In this article, Takahashi and colleagues show the allogeneic immune response, such as immune rejection, to iPSC-derived retinal pigment epithelial (RPE) cells by inflammatory cells in vivo. However, the immune reaction does not occur when iPS-RPE cells established from MHC homozygous donors were transplanted.
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