Organoid-induced differentiation of conventional T cells from human pluripotent stem cells
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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http://data.iscr.ac.cn/Article?id=fd3c700a7e3975fe0aab2e8529b2b24c
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Generation of T cells from pluripotent stem cells (PSC) has the potential to transform adoptive immunotherapy for cancer into universal donor, off-the-shelf cellular therapies. However, differentiation of human PSCs into fully mature T cells has been challenging with existing methods. We report that a 3D organoid method permitted efficient differentiation of human embryonic stem cell and induced pluripotent stem cell-derived mesoderm progenitors to mature, functional conventional T cells with a diverse T cell receptor (TCR) repertoire. This continuous culture system supported both hematopoietic induction and terminal differentiation to naïve, conventional CD3+CD8αβ+ and CD3+CD4+ T cells. Introduction of a Class I-restricted TCR in PSCs produced antigen-specific CD8αβ+ T cells lacking endogenous TCR expression. Functional assays and RNA sequencing aligned PSC-derived T cells with primary naïve conventional CD8+ T cells. The organoid system presented here provides an effective and scalable platform to generate functional mature T cells from human PSCs.
提供机构:
University of California Los Angeles
创建时间:
2022-02-20



