期刊
CELL STEM CELL
卷 24, 期 3, 页码 376-+出版社
CELL PRESS
DOI: 10.1016/j.stem.2018.12.011
关键词
-
资金
- NIH/NCATS [KL2TR001882]
- Broad Stem Cell Research Center Clinical Fellowship
- Tower Cancer Research Foundation Career Development Grant
- National Cancer Institute of the NIH [P30CA016042]
- UCLA Center for AIDS Research Virology Core Lab
- Kite Pharma/Gilead Biosciences
- NIH/NHLBI [T32HL066992]
- UCLA AIDS Institute [5P30 AI028697]
The ability to generate T cells from pluripotent stem cells (PSCs) has the potential to transform autologous T cell immunotherapy by facilitating universal, off-the-shelf cell products. However, differentiation of human PSCs into mature, conventional T cells has been challenging with existing methods. We report that a continuous 3D organoid system induced an orderly sequence of commitment and differentiation from PSC-derived embryonic mesoderm through hematopoietic specification and efficient terminal differentiation to naive CD3(+) CD8 alpha beta(+) and CD3(+) CD4(+) conventional T cells with a diverse T cell receptor (TCR) repertoire. Introduction of an MHC class I-restricted TCR in PSCs produced naive, antigen-specific CD8 alpha beta(+) T cells that lacked endogenous TCR expression and showed anti-tumor efficacy in vitro and in vivo. Functional assays and RNA sequencing aligned PSC-derived T cells with primary naive CD8(+) T cells. The PSC-artificial thymic organoid (ATO) system presented here is an efficient platform for generating functional, mature T cells from human PSCs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据