Researchers modified existing organ tissue to create a miniature three-dimensional colon with immune cells, which could help develop personalized treatments for colon-related diseases such as inflammatory bowel disease and cancer.
The study of healthy organs and their disease states is critical to our understanding of both and the development of new and effective treatments. Miniature three-dimensional organs, or organoids, can be used to study disease mechanisms in tissues that closely resemble the real thing. However, many organ tissues are missing an important component that most organs have: a connection to the immune system.
Now, researchers at the Medical University of South Carolina Hollins Cancer Center, in collaboration with Cincinnati Children's Hospital Medical Center, have solved this problem by developing a colon organoid with immune cells.
"We think this new model is significant because most gastrointestinal diseases involve the immune system and inflammation."
A diverse population of immune cells exists in the gastrointestinal tract. Most intestinal diseases, especially inflammatory bowel disease (IBD), involve the immune system, so it is important to obtain these cells when conducting research.
Researchers directed human pluripotent stem cells (hPSCs) to differentiate into human colon organ tissue. These cells self-organize into layers similar to native intestinal tissue and together develop a variety of immune cells, including hematopoietic endothelial-like cells that give rise to functional macrophages. Macrophages are specialized immune cells that sense and respond to pathogens in addition to initiating, sustaining, and eliminating inflammation.
"Importantly, these immune cells are nearly identical to those found in humans and are capable of detecting disease-causing bacteria and clearing them out," said James Wells, corresponding author of the study. "This is an important step for research aimed at identifying future treatments for intestinal diseases and other conditions affecting the gastrointestinal tract."
The researchers say their mini-colon is closer to a human colon.
"They (organ tissues) contain not only the lining of the colon, but also supporting cells and even some immune cells that grow with other tissues in the colon," said Dr. Jorge Munera. "We made a more complete human organoid system that can be used to model colon inflammation."
The researchers believe that, with further development, their new organoids could be used to help personalize treatments for colon diseases. For example, these organoids could be generated from the blood of patients with early-stage IBD and used to test whether treatments are working before proceeding with them.
The research was published in the journal CellStemCell.