Medical breakthrough: Mini human guts grown inside mice

Michael Helmrath, a pediatric surgeon at Cincinnati Children’s Hospital Medical Center, and his colleagues made headlines last week when they revealed trials where they had transplanted balls of human intestinal tissue into mice, according to a report by Wired published on Thursday.

After a few weeks, these transplants developed key features of the human immune system, introducing a model that could be used to effectively simulate the human intestinal system.

It’s not the first time researchers at Cincinnati Children’s make such an advancement in organoids (miniature replicas of human organs). In 2010, the institution became the first in the world to create a working intestinal organoid.

Containing human cells

Since organoids contain human cells and exhibit some of the same structures and functions as real organs, scientists everywhere are using them to study how organs develop, how diseases occur and how drugs work.

“It’s incredibly important that when we are trying to create these platforms for testing drug efficacy and drug side effects in human tissue models that we actually make sure that we are as close to, and as complete as, the tissue in which the drug will work eventually in our human body. So, adding the immune system is an important part of that,” told Wired Pradipta Ghosh, director of the Humanoid Center of Research Excellence at the University of California San Diego School, which is engineering human organoids to test drugs. Ghosh was not part of the new study.

Helmrath and his team started with induced pluripotent stem cells, which can turn into any type of body tissue, and fed them a specific molecular cocktail to coax them into transforming into intestinal cells. They ended up with some organoid spheres that the team then carefully transplanted into mice.

20 types of human immune cells

After 20 weeks, the organoids were found to contain around 20 types of human immune cells. “That is very similar to the populations we see in the human gut,” told Wired Helmrath. 

The team then wanted to test whether the immune cells actually functioned so they exposed the organoids to E. Coli bacteria. This resulted in the production of M cells, immune signaling cells found in the lining of the gut that are normally spurred by infection and inflammation.

The researchers now hope that their organoids could one day be used to help people born with genetic defects in their digestive systems or those who have somehow lost intestinal function. They also believe that the organoids might just be able to grow on their own if transplanted into a human. 

The study is published in the journal Nature Biotechnology.

Study Abstract:

Human intestinal organoids (HIOs) derived from pluripotent stem cells provide a valuable model for investigating human intestinal organogenesis and physiology, but they lack the immune components required to fully recapitulate the complexity of human intestinal biology and diseases. To address this issue and to begin to decipher human intestinal–immune crosstalk during development, we generated HIOs containing immune cells by transplanting HIOs under the kidney capsule of mice with a humanized immune system. We found that human immune cells temporally migrate to the mucosa and form cellular aggregates that resemble human intestinal lymphoid follicles. Moreover, after microbial exposure, epithelial microfold cells are increased in number, leading to immune cell activation determined by the secretion of IgA antibodies in the HIO lumen. This in vivo HIO system with human immune cells provides a framework for future studies on infection- or allergen-driven intestinal diseases.