Journal article
De novo construction of T cell compartment in humanized mice engrafted with iPSC-derived thymus organoids
NATURE METHODS, v 19(10), p1306
Oct 2022
PMID: 36064772
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 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. Engraftment of human thymic organoids supports de novo development of a functional human T cell compartment in a humanized mouse model.
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Details
- Title
- De novo construction of T cell compartment in humanized mice engrafted with iPSC-derived thymus organoids
- Publication Details
- NATURE METHODS, v 19(10), p1306
- Publisher
- NATURE PORTFOLIO; BERLIN
- Grant note
- We thank E. Moravcikova for support with FCM, A. Sanguino for assistance with pathological assessment of teratomas, D. Graziano for assistance with HLA typing, H. Monroe and the University of Pittsburgh Genomics Research core for their expertise in scRNA preparation and analysis, and B. Phillips and W. Rudert for insightful suggestions and discussions of the project. Figure 3a was created with BioRender.com. This study was supported in part by the National Institutes of Health (grant nos. Y.F., R01 AI123392 and R21 AI126335), National Science Foundation (Y.F. and I.B., CBET, standard grant no. 1804728), PA Health Department research grant (M.T., SAP no. 4100079708). C.M. and H.G. were supported by Highmark Health Award (grant no. A023948-HIGHMARK-LANNI-FAN). We also thank the Center for Biologic imaging University of Pittsburgh for the use of imaging facilities under the grant no. 1S10OD019973-01.
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University
- Web of Science ID
- WOS:000850014200002
- Scopus ID
- 2-s2.0-85137452813
- Other Identifier
- 991021861279504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemical Research Methods