Research Horizons


First the Small Intestine, Now the Colon has an Organoid with an Immune System

A multicenter team led by experts at Cincinnati Children’s and the Medical University of South Carolina has developed a next-generation colon organoid that includes resident immune cells.

These mini-organs, grown from human pluripotent stem cells, can serve as sophisticated models for studying the diseased colon and could lead to personalized treatments for colon-related diseases, such as cancer and inflammatory bowel disease (IBD).

The study, published Nov. 2, 2023, in Cell Stem Cell, was led by first and corresponding author Jorge Munera, PhD, of the MUSC Hollings Cancer Center; co-first author Daniel Kechele, PhD, Division of Developmental Biology at Cincinnati Children’s; and co-corresponding author James Wells, PhD, chief scientific officer for the Cincinnati Children’s Center for Stem Cell and Organoid Medicine (CuSTOM).

This model improves upon earlier generations of organoids that have lacked immune components.

“We think that this new model is significant because most gastrointestinal diseases involve the immune system and inflammation,” Munera says.

This study builds upon breakthrough work involving the small intestine that was published online Jan. 26, 2023 in Nature Biotechnology. That study, led by Michael Helmrath, MD, at Cincinnati Children’s and co-authored by Wells and colleagues, was the first reported in vivo organoid of any type (heart, liver, stomach, etc.) to incorporate a functional immune system.

Importantly, these immune cells are nearly identical to those found in the human body, where they are able to detect disease-causing bacteria and remove them,” Wells says. “This is an important step for research aimed at identifying future therapies for IBD and other diseases, impacting the gastrointestinal tract.”

In addition to Wells, co-authors from Cincinnati Children’s and the University of Cincinnati included co-first author Daniel Kechele, Carine Bouffi, Jacob Enriquez, Ian Campbell, Maxime Mahe, Heather McCauley, Xinghao Zhang, Nambirajan Sundaram, Jonathan Hudson, Adrian Zarsozo-Lacoste, Suman Pradhan, Kentaro Tominaga, J. Guillermo Sanchez, Alison Weiss, Praneet Chatuvedi, Christopher Mayhew, Yueh-Chiang Hu, Takanori Takebe and Michael Helmrath.



Read More About Organoid Research at Cincinnati Children’s

Publication Information
Original title: Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon
Published in: Cell Stem Cell
Publish date: Nov. 2, 2023
Read the Findings

Research By

James Wells, PhD
James Wells, PhD
Chief Scientific Officer, Center for Stem Cell and Organoid Medicine (CuSTOM)

Research in the Wells lab aims to uncover the molecular and cellular mechanisms by which gastrointestinal and endocrine organs form in the developing embryo.