Tuft Cells: A New Hope for Gut Healing

Immunological cues cause intestinal tuft cells to proliferate and create new cells. Furthermore, tuft cells can withstand severe damage, such as radiation damage, and aid in the regeneration of the epithelium, in contrast to progenitor- and stem cells.

That is what researchers from the Hubrecht Institute’s Organoid group discovered using lab-grown miniature human intestines. The findings, which were published in Nature on October 2^nd, 2024, could have significant implications for the regeneration of damaged intestinal tissue.

The human intestinal tract regulates nutrient absorption and hormone production and protects the gut from pathogens. These important functions are carried out by specialized cells in the epithelium, the tissue that lines the intestines. The epithelium is made up of several types of specialized epithelial cells, including tuft cells.

The Function of Tuft Cells

Tuft cells can be found in many organs, including the intestinal tract. Mice research has provided the majority of insights into the function and ontology of these cells. Studies have shown that one type of tuft cell protects the gut from pathogens.

When tuft cells detect pathogens, they send signals to immune cells and the epithelium, triggering a strong defense response. However, because of a lack of human research models, the function of tuft cells in the human intestinal tract was unknown.

Miniature Intestines

This is more than sufficient justification for the Organoid group’s researchers to investigate this topic further using the special organoid technology they created. In a dish, they cultivated tiny intestines that imitate the way real human intestines work. The various intestinal cell types are all present in the structures, which are also referred to as organoids.

We used these organoids to carefully monitor the development and function of tuft cells. Moreover, this model enabled us to study the effect of radiation on the function of the organoids.”

Lulu Huang, Study Co-First Author and PhD Student, Hubrecht Institute

Tuft Cells Act as Reserve Stem Cells

One of the most significant findings of the study was the ability of tuft cells to multiply in response to immunological stimuli.

Upon receiving such immunological signals, tuft cells divide to make new tuft cells, which can in turn transdifferentiate and generate all other epithelial cell types. Through this process, tuft cells can restore the wounded gut.”

Jochem Bernink, Post Doctoral Researcher, Hubrecht Institute

Survival After Damage

The ability of tuft cells to withstand radiation damage is particularly remarkable. Tuft cells can survive and give rise to all the different types of intestinal epithelial cells in cases where stem- and progenitor cells are unable to proliferate following such damage.

Huang added, “We also grew organoids without tuft cells, and these organoids were unable to recover from radiation damage.”

Consequently, tuft cells are crucial for the regeneration of damaged intestinal tissue.

Regeneration of Tissue

“Tuft cells basically form a pool of reserve stem cells in the human intestines. A pool that is brought to action when damage has occurred,” Bernink stated.

The results, which were published in Nature, might have an impact on the field of regenerative medicine, which studies tissue regeneration and repair.

“In addition to more research into the exact regenerative function of human tuft cells, it would be interesting to study the function of tuft cells in other organs, for example in the liver, urinary tract and lungs,” Huang concluded.