Investigators uncover small molecule to engineer intestinal cell types


Date:
March 22, 2022
Source:
Brigham and Women's Hospital
Summary:
Investigators have created specialized, tissue-like structures in
the laboratory to model barrier tissues, such as the intestines,
to identify new targets for treatment.



FULL STORY ========================================================================== Investigators at the Brigham and the Broad Institute have created
specialized, tissue-like structures in the laboratory to model
barrier tissues, such as the intestines, to identify new targets
for treatment. Barrier tissues are exposed to substances from the
outside world but serve as a layer of protection. Over the years,
researchers have developed more sophisticated, three-dimensional models
of epithelial barrier tissues, such as the intestine. These models are
known as intestinal organoids. In a new study, investigators discovered
a tissue-modifying molecule that can target intestinal stem cells and
signal them to create Paneth cells, a rare but important cell type that
can alter the gut microbiota. Previous studies have shown that Paneth
cells are depleted in diseases such as inflammatory bowel disease and graft-versus-host disease.

Replenishing these rare cells could represent a new therapeutic
pathway. The team's approach could also be used to identify molecules
that could target other intestinal cell types.


==========================================================================
"Our paper provides the first approach to engineering our barrier tissues
like the intestine by targeting and activating stem cells in situand
causing new important cell types to form," said co-lead author Benjamin
Mead, PhD, of the Broad Institute. "This could be used to potentially
treat a wide range of diseases by manipulating the cell composition of the intestine." "This approach has wide ranging implications and can be used
to manipulate the cellular makeup of the intestine, including cells that
can enhance barrier function, produce gut hormones, or that have key roles
in coordinating insulin levels as well as food digestion and absorption,"
said co-corresponding author Jeff Karp, PhD, Distinguished Chair in
Clinical Anesthesiology, Perioperative and Pain Medicine. "This approach
also enables a completely new strategy to manipulate gut microbiota and
thus offer insights into the treatment of a wide range of diseases."

========================================================================== Story Source: Materials provided by Brigham_and_Women's_Hospital. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Benjamin E. Mead, Kazuki Hattori, Lauren Levy, Shinya Imada,
Norihiro
Goto, Marko Vukovic, Daphne Sze, Conner Kummerlowe, Juan
D. Matute, Jinzhi Duan, Robert Langer, Richard S. Blumberg,
Jose Ordovas-Montanes, O"mer H. Yilmaz, Jeffrey M. Karp, Alex
K. Shalek. Screening for modulators of the cellular composition
of gut epithelia via organoid models of intestinal stem cell
differentiation. Nature Biomedical Engineering, 2022; DOI:
10.1038/s41551-022-00863-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220322150918.htm

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