Lack of Immune Response to Differentiated Cells Derived from Syngeneic Induced Pluripotent Stem Cells

Lack of Immune Response to Differentiated Cells Derived from Syngeneic Induced Pluripotent Stem Cells
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DOI:
10.1016/j.stem.2013.01.006
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发表时间:
2013-04-04
期刊:
影响因子:
23.9
通讯作者:
Boyd, Ashleigh S.
Boyd, Ashleigh S.
中科院分区:
医学1区
文献类型:
--
作者:
Guha, Prajna;Morgan, John W.;Boyd, Ashleigh S.

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在细胞替代疗法中使用自体诱导多能干细胞(iPSC)的前景已经被未分化的同基因小鼠iPSC在移植后具有免疫原性的证据所缓和。然而,更多的治疗相关的分化细胞的免疫原性仍然没有探索。在这里,我们将小鼠iPSCs分化为胚状体(EB)或跨越三个胚胎胚层的代表性细胞类型,并在体外和移植到同基因受体后评估其免疫原性。我们没有发现体外T细胞增殖增加,移植后同源iPSC衍生的EB/组织特异性细胞(TSC)排斥或抗原特异性二次免疫应答的证据。因此,来源于同基因iPSC的分化细胞在移植后似乎不会被排斥。我们还发现几乎没有证据表明对未分化的同基因iPSC的免疫应答。我们的数据支持这样的想法,即从自体iPSC产生的分化细胞可以用于细胞替代疗法,而不会引发免疫排斥反应。
The prospects for using autologous induced pluripotent stem cells (iPSCs) in cell replacement therapy have been tempered by evidence that undifferentiated, syngeneic mouse iPSCs are immunogenic upon transplantation. However, the immunogenicity of more therapeutically relevant differentiated cells remains unexplored. Here, we differentiated mouse iPSCs into embryoid bodies (EBs) or representative cell types spanning the three embryonic germ layers and assessed their immunogenicity in vitro and after their transplantation into syngeneic recipients. We found no evidence of increased T cell proliferation in vitro, rejection of syngeneic iPSC-derived EBs/tissue-specific cells (TSCs) after transplantation, or an antigen-specific secondary immune response. Thus, differentiated cells derived from syngeneic iPSCs do not appear to be rejected after transplantation. We also found little evidence of an immune response to undifferentiated, syngeneic iPSCs. Our data support the idea that differentiated cells generated from autologous iPSCs could be applied for cell replacement therapy without eliciting immune rejection.