Research into healthy organs and their disease states is crucial to our understanding of both and the development of new and effective treatments. Miniature 3D versions of organs, or organoids, can be used to study disease mechanisms in tissue closely resembling the real thing. However, many organoids are missing a crucial component that most organs have IRL: connection to an immune system.

Now, researchers at the Medical University of South Carolina (MUSC) Hollings Cancer Center, in collaboration with the Cincinnati Children's Hospital Medical Center, have addressed that issue by developing a colon organoid complete with immune cells.

"We think that this new model is significant because most gastrointestinal diseases involve the immune system and inflammation," said Jorge Múnera, lead author of the study.

Diverse populations of immune cells populate the gastrointestinal tract. Most intestinal diseases, particularly inflammatory bowel diseases (IBDs), involve the immune system, which makes it important to have access to these cells when conducting research.

The researchers directed the differentiation of human pluripotent stem cells (hPSCs) to generate human colonic organoids. The cells self-organized into layers similar to natural gut tissue and co-developed a diverse population of immune cells, including hemogenic endothelium-like cells that generated functional macrophages. Macrophages are specialized immune cells that sense and respond to pathogens in addition to initiating, maintaining, and resolving inflammation.

"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," said James Wells, a corresponding author of the study. "This is an important step for research aimed at identifying future therapies for IBD and other diseases impacting the gastrointestinal tract."