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Title: De novo construction of T cell compartment in humanized mice engrafted with iPSC-derived thymus organoids
Hematopoietic humanized (hu) mice are powerful tools for modeling the function of the human immune system and are also widely used for preclinical and drug discovery studies. However, generating a functional human T cell compartment in hu mice remains challenging, primarily due to the species-related differences between human and mouse thymus. While engrafting human fetal thymic tissues can support robust T cell development in hu mice, tissue scarcity and ethical concerns limit their wide use. Here, we describe tissue engineered human thymus organoids generated from inducible pluripotent stem cells (iPSC-thymus) that can support the de novo generation of a diverse population of functional human T cells. T cells of iPSC-thymus engrafted hu mice could mediate both cellular and humoral immune responses, including mounting robust proinflammatory responses upon TCR engagement, inhibiting allogeneic tumor graft growth and facilitating efficient Ig class switching. Our findings suggest that hu mice engrafted with iPSC-thymus can work as a novel system to study the development and function of human T cells in vivo.  more » « less
Award ID(s):
1804728
PAR ID:
10355689
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
Editor(s):
Madhura Mukhopadhyay
Date Published:
Journal Name:
Nature Methods
ISSN:
1548-7091
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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