Kentaro Tominaga, Daniel O. Kechele, J. Guillermo Sanchez, Simon Vales, Ingrid Jurickova, Lizza Roman, Akihiro Asai, Jacob R. Enriquez, Heather A. McCauley, Keishi Kishimoto, Kentaro Iwasawa, Akaljot Singh, Yuko Horio, Jorge O. Múnera, Takanori Takebe, Aaron M. Zorn, Michael A. Helmrath, Lee A. Denson, and James M. Wells
Deriving Human Intestinal Organoids with Functional Tissue Resident Macrophages All From Pluripotent Stem Cells
- Field of Research：inflammatory|organoid
- Research Methods：IF|FC
- Species：human
- Sample Type：human intestinal organoids
- Models：human intestinal organoids
- Journal：Cell Mol Gastroenterol Hepatol
- Time：2025
- Product line：organoid
- Key words：
human intestinal organoids、iPSC、macrophages
Abstract
Organs of the gastrointestinal tract contain tissue-resident immune cells that function during tissue development, homeostasis, and disease. However, most published human organoid model systems lack resident immune cells, thus limiting their potential as disease avatars. For example, human intestinal organoids (HIOs) derived from pluripotent stem cells contain epithelial and various mesenchymal cell types but lack immune cells. In this study, we aimed to develop an HIO model with functional tissue-resident macrophages.
Macrophages were incorporated into developing HIOs and persisted for 2 weeks in vitro HIOs and for at least 12 weeks in HIOs in vivo. These cocultured macrophages had a transcriptional signature that resembled those in the human fetal intestine, indicating that they were acquiring the features of tissue-resident macrophages. HIO macrophages could phagocytose bacteria and produced inflammatory cytokines in response to proinflammatory signals, such as lipopolysaccharide, which could be reversed with interleukin-10.
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