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

Autor: Ann Zeleniak, Connor Wiegand, Wen Liu, Catherine McCormick, Ravikumar K., Amir Alavi, Haonan Guan, Suzanne Bertera, Robert Lakomy, Asako Tajima, Henry Cohen, Stephanie Wong, Lame Balikani, Benjamin Mizerak, Ziv Bar-Joseph, Massimo Trucco, Ipsita Banerjee, Yong Fan
Rok vydání: 2022
Předmět:
Zdroj: Nature Methods. 19:1306-1319
ISSN: 1548-7105
1548-7091
Popis: 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 on T cell receptor engagement, inhibiting allogeneic tumor graft growth and facilitating efficient Ig class switching. Our findings indicate that hu mice engrafted with iPSC-thymus can serve as a new animal model to study human T cell-mediated immunity and accelerate the translation of findings from animal studies into the clinic.
Databáze: OpenAIRE
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