Mini Human Guts Transplanted Into Mice Developed Key Features of Immune System [Study]

A new study was able to grow organoids inside mice with working immune systems that mimic the function of the GI tract.

Human Intestinal Tissue Place Inside Mice

Michael Helmrath, a pediatric surgeon at Cincinnati Children's Hospital Medical Center who treats patients with intestinal diseases, and his colleagues announced in the journal Nature Biotechnology that they experimented with studying the human immune system through mice last week. They transplanted tiny, three-dimension balls of human intestinal tissue into mice.

After several weeks, the spheres - known as organoids - developed key features of the human immune system. They are great models for studying the human intestinal system without experimenting with sick patients, Wired reported.

The experiment was a follow-up from 2010 when researchers at Cincinnati Children's became the first to create a working intestine organoid. Their model was a simple version of a lab dish at the time.

Over a decade later, Helmrath said they had to make it like human tissue.

Other scientists have also used the approach of growing small replicas of human organs. They use miniature of the brain, lungs, and liver to understand better how they develop normally and how things go amiss, leading to the development of diseases.

Organoids are often employed in pharmacological testing as human avatars. Due to the fact that they include human cells and exhibit some of the same structures and functions as genuine organs, some researchers believe that they are a superior substitute to laboratory animals.

When attempting to construct these platforms for assessing medication efficacy and drug side effects in human tissue models, it is of the utmost importance to ensure that they are as near to and as comprehensive as the tissue in which the drug will eventually work in the human body, according to Pradipta Ghosh, director of the Humanoid Center of Research Excellence at the University of California, San Diego, which is building human organoids to screen and test pharmaceuticals, integrating the immune system is crucial. Ghosh did not contribute to the study.

How Did They Cultivate, Test The Organoids?

To cultivate the organoid, scientists began with induced pluripotent stem cells derived from adult human blood or skin cells. They are capable of transforming into any bodily tissue. The team encouraged stem cells to transform into intestinal cells using a special chemical cocktail. After 28 days, the cells created tissue spheres measuring only a few millimeters in diameter.

The team transplanted these spheres into mice that had been genetically modified to suppress their immune systems to ensure that the organoid would not be rejected. They placed it close to the kidneys of each mouse so it was not attached to the animal's digestive tracts. In order to encourage the organoids to produce human immune cells, they administered human cord blood to the mice as a source of stem cells that could transform into the desired cells.

After 20 weeks, each organoid grew into the size of a pea and contained approximately 20 distinct types of human immune cells. According to Helmrath, it was similar to the populations they observed in the human gut. At that time, the organoids had also developed human lymphoid follicles, commonly known as Peyer's patches, which are essential structures in the intestine that keep pathogens at bay by maintaining healthy bacteria levels.

Ghosh considered the structures of the tonsils to the gut because they prevent pathogens from making us sick. Other researchers have added immune cells to organoids grown in a laboratory dish, but according to Ghosh, the Cincinnati team is the only one to take the further steps of transplanting them into an animal such that they produce functional components of the human immune system, including follicles.

The researchers subjected the organoids to the E. Coli bacteria, widely present in the human colon, to determine whether the immune cells were functional. Later, they discovered that the Peyer's patches produced M cells, which are immunological signalling cells found in the gut lining. This, according to Helmrath, suggests that the organoids' immune system could react to the presence of germs. Prior research has demonstrated that infection and inflammation stimulate the development of M cells.

The organoids flourishing in a mouse is a sign that they can grow on their own when transplanted into a person. Helmrath's next goal is to make organoids from patients' cells to test individualized therapies.

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