New organoid model could lead to personalized treatments for colon-related diseases

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A team from the Medical University of South Carolina and Cincinnati Children’s has developed a sophisticated model to study the diseased colon that could lead to the development of personalized treatments for colon-related diseases, such as cancer and inflammatory bowel disease (IBD). The researchers reported their findings in November. 2 numbers Cells are stem cells.

MUSC Hollings Cancer Center researchers Jorge Munera, Ph.D., James Wells, Ph.D., and Daniel Kechele, Ph.D., both of Cincinnati Children’s, collaborated to grow miniature human colons complete with an immune system in the lab. . This model improves upon existing organoids, or small organs, that have no natural connection with immune components These new colon organoids more closely resemble the human colon in both healthy and diseased states.

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

George Munera, PhD, Assistant Professor, Department of Regenerative Medicine and Cell Biology at MUSC

Until recently, methods for studying colon diseases such as colon cancer and IBD were limited to cells and animal models. The cells are often derived from cancerous tumors, which limits their applicability in the study of non-cancerous diseases. Animal models have their own limitations: promising treatments in animals do not always provide the same benefits in humans.

A happy medium between cells and organisms is provided by organoids, three-dimensional groups of cells that mimic the function of organs. They are significantly more complex than traditional human cell cultures, but they still lack some of the features of whole human organs, and unlike an animal model, organoids are not connected to whole body systems.

Munera, Wells, and their team found a way to overcome a significant residual limitation of colon organoids by inducing these next-generation organoids to develop early stage immune cell types that normally reside within colon tissue.

The study builds on similar work published online in January. 26, in 2023 nature biotechnology, It was led by Michael Helmrath, MD, of Cincinnati Children’s and co-authored by Wells and colleagues.

“Importantly, these immune cells are almost identical to those found in the human body, where they are able to identify and eliminate disease-causing bacteria,” Wells said. “This is an important step for research aimed at identifying future therapies for IBD and other diseases that affect the gastrointestinal tract.”

The research team created colon organoids using stem cells obtained from patient blood samples. Stem cells are identical progenitor cells in the body that can develop into specific cell types needed by the body. Under the right conditions, these stem cells can communicate with each other to form a colon organoid. Cell communication allows them to self-organize at levels similar to natural tissue organization in the body.

“They contain not only the lining of the colon but also supportive cells and even some immune cells that grow with the rest of this tissue,” Munera explained.

Immune cells in these new colon organoids are part of the innate immune system and act as the body’s “first responders” to inflammation.

“We’ve created a more complete human organoid system that we can use to model inflammation in the colon,” Munera said.

With further development, Munera believes the novel organoid model could help personalize treatment for colon disease. In the future, these organoids could be made from the blood of an early-onset IBD patient, for example, and used to test whether a treatment will work before administering it.


Journal Reference:

Munera, J.O., etc (2023). Development of human pluripotent stem cell-derived colonic organoids and functional resident macrophages in the human fetal colon. Cells are stem cells.

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