Human pluripotent stem cell-derived organoids repair damaged bowel in vivo

The fundamental goal of tissue engineering is to functionally restore or improve damaged tissues or organs. Here we address this in the small bowel using an in vivo xenograft preclinical acute damage model. We investigated the therapeutic capacity of human intestinal organoids (HIOs), which are gene...

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Bibliographic Details
Published in:	Cell stem cell Vol. 31; no. 10; p. 1513
Main Authors:	Poling, Holly M, Sundaram, Nambirajan, Fisher, Garrett W, Singh, Akaljot, Shiley, Joseph R, Nattamai, Kalpana, Govindarajah, Vinothini, Cortez, Alexander R, Krutko, Maksym O, Ménoret, Séverine, Anegon, Ignacio, Kasendra, Magdalena, Wells, James M, Mayhew, Christopher N, Takebe, Takanori, Mahe, Maxime M, Helmrath, Michael A
Format:	Journal Article
Language:	English
Published:	United States 03-10-2024
Subjects:	Animals Humans Intestine, Small - cytology Mice Organoids Pluripotent Stem Cells - cytology Pluripotent Stem Cells - metabolism Rats Regeneration tissue regeneration enteroid intestine human intestinal organoid cell therapy
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Summary:	The fundamental goal of tissue engineering is to functionally restore or improve damaged tissues or organs. Here we address this in the small bowel using an in vivo xenograft preclinical acute damage model. We investigated the therapeutic capacity of human intestinal organoids (HIOs), which are generated from human pluripotent stem cells (hPSCs), to repair damaged small bowel. We hypothesized that the HIO's cellular complexity would allow it to sustain transmural engraftment. To test this, we developed a rodent injury model where, through luminal delivery, we demonstrated that fragmented HIOs engraft, proliferate, and persist throughout the bowel following repair. Not only was restitution of the mucosal layer observed, but significant incorporation was also observed in the muscularis and vascular endothelium. Further analysis characterized sustained cell type presence within the regenerated regions, retention of proximal regionalization, and the neo-epithelia's function. These findings demonstrate the therapeutic importance of mesenchyme for intestinal injury repair.
ISSN:	1875-9777
DOI:	10.1016/j.stem.2024.08.009