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De novo construction of T cell compartment in humanized mice engrafted with iPSC-derived thymus organoids

ABSTRACT: Hematopoietic humanized (hu) mice are powerful tools for modeling the action of human immune system and are widely used for preclinical studies and drug discovery. 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 the tissue engineering of human thymus organoids 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 the growth of allogeneic tumor grafts and facilitating efficient Ig class switching. Our findings suggest that hu mice engrafted with iPSC-thymus can serve as a novel animal model to study human T cell-mediated immunity and accelerate the translation of animal studies into the clinic.

ORGANISM(S): Homo sapiens

PROVIDER: GSE201675 | GEO | 2022/05/31

REPOSITORIES: GEO

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De novo construction of T cell compartment in humanized mice engrafted with iPSC-derived thymus organoids

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