In vivo development of immune tissue in human intestinal organoids transplanted into humanized mice

被引：84

作者：

Bouffi, Carine ^{[1
]}

Wikenheiser-Brokamp, Kathryn A. ^{[2
,3
]}

Chaturvedi, Praneet ^{[4
,5
]}

Sundaram, Nambirajan ^{[1
]}

Goddard, Gillian R. ^{[1
]}

Wunderlich, Mark ^{[6
]}

Brown, Nicole E. ^{[1
]}

Staab, Janet F. ^{[7
]}

Latanich, Rachel ^{[7
]}

Zachos, Nicholas C. ^{[7
]}

Holloway, Emily M. ^{[8
]}

Mahe, Maxime M. ^{[1
,8
,9
]}

Poling, Holly M. ^{[1
]}

Vales, Simon ^{[1
]}

Fisher, Garrett W. ^{[1
]}

Spence, Jason R. ^{[10
,11
]}

Mulloy, James C. ^{[5
]}

Zorn, Aaron M. ^{[4
,5
]}

Wells, James M. ^{[4
,5
]}

Helmrath, Michael A. ^{[1
,5
,9
]}

机构：

[1] Cincinnati Childrens Hosp Med Ctr, Div Pediat Gen & Thorac Surg, Cincinnati, OH 45229 USA

[2] Cincinnati Childrens Hosp Med Ctr, Div Pathol & Lab Med, Cincinnati, OH USA

[3] Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH USA

[4] Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Cincinnati, OH USA

[5] Cincinnati Childrens Hosp Med Ctr, Ctr Stem Cell & Organoid Med CuSTOM, Cincinnati, OH 45229 USA

[6] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH USA

[7] Johns Hopkins Univ, Dept Med, Div Gastroenterol & Hepatol, Sch Med, Baltimore, MD USA

[8] Univ Nantes, Inserm, TENS, Enter Nervous Syst Gut & Brain Dis, Nantes, France

[9] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA

[10] Univ Michigan, Dept Internal Med, Dept Cell & Dev Biol, Div Gastroenterol,Med Sch, Ann Arbor, MI USA

[11] Univ Michigan, Dept Biomed Engn, Coll Engn, Ann Arbor, MI 48109 USA

来源：

NATURE BIOTECHNOLOGY | 2023年 / 41卷 / 06期

基金：

美国国家卫生研究院;

关键词：

PLURIPOTENT STEM-CELLS;

D O I：

10.1038/s41587-022-01558-x

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Human intestinal organoids are endowed with immune cells by transplantation into humanized mice. Human intestinal organoids (HIOs) derived from pluripotent stem cells provide a valuable model for investigating human intestinal organogenesis and physiology, but they lack the immune components required to fully recapitulate the complexity of human intestinal biology and diseases. To address this issue and to begin to decipher human intestinal-immune crosstalk during development, we generated HIOs containing immune cells by transplanting HIOs under the kidney capsule of mice with a humanized immune system. We found that human immune cells temporally migrate to the mucosa and form cellular aggregates that resemble human intestinal lymphoid follicles. Moreover, after microbial exposure, epithelial microfold cells are increased in number, leading to immune cell activation determined by the secretion of IgA antibodies in the HIO lumen. This in vivo HIO system with human immune cells provides a framework for future studies on infection- or allergen-driven intestinal diseases.

引用

页码：824 / +

页数：26

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