Biomedical Research

Mini-intestines grown in vitro

26.11.2015 | The growing of three-dimensional organ precursors from stem cells has brought about a revolution in the field of biomedicine. A team from the Technical University of Munich has now shown how artificially grown mini-intestines can be used in nutritional and diabetic research.
The human intestine has the approximate surface area of a one-room flat, and it contains a number of neurons comparable to the human brain: this is why the intestine is sometimes referred to as the 'abdominal brain'. In addition to absorbing nutrients from the food we eat, it influences our immune status and metabolism. With the help of sensors, specialized cells in the intestinal wall determine which hormones should be released into the bloodstream. Overall, it acts as a highly sophisticated control centre.

Intestinal hormones, known as incretins, control blood glucose levels, appetite and fat metabolism, among other functions. Diabetics and obese individuals have already been successfully treated with drugs based on the metabolism of these hormones. But how does the mechanism behind incretin release work in detail?

An Organoid
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An Organoid
Using a new method from stem-cell research and regenerative medicine, researchers from the Technical University of Munich (TUM) have now devised an efficient intestinal model for molecular research into incretin release. First they isolated small pieces of intestine containing stem cells, in this case from mice. In a next step, a nutrient solution stimulated these stem cells to develop into an organ-like structure. In just a few days, a spherical organoid formed, measuring only a quarter of a millimeter across and exhibiting all essential functions of a normal working intestine.

"The special thing about our scientific work on the intestinal organoid is that we can observe its inner workings," explains Dr. Tamara Zietek of the Department of Nutrition Physiology. "The mini-intestines exhibit all the essential functions of a real intestine," the TUM scientist adds. The intestinal organoid can actively absorb nutrients and drugs, release hormones after activation by nutrients transmit signals within the intestinal cells to control these processes. "Until now, it was not possible to investigate these processes in a single model, because conventional models are unsuitable for all these measurements," Tamara Zietek explains, corresponding author of the paper that appeared in Nature Scientific Reports.

Because these mini-intestines can be replicated in the lab, the researchers can work with them for several months. "This drastically reduces the number of experimental animals needed," says the scientist. Zietek developed the method together with Dr. Eva Rath of the Department of Nutrition and Immunology. The two researchers have combined organoid cultivation with molecular nutritional research. They are now demonstrating that the mini-intestine is an ideal model for investigating hormone release and transport mechanisms in the digestive tract.

"This is a huge advance for gastroenterological basic research as well as biomedical sciences and pharmacology," Zietek believes. The next step will be to work with mini-intestines grown from human intestinal biopsy material. "We're already in contact with a hospital that can provide the required research material," says TUM-scientist, giving insights into the department's future research strategies.

Prof. Hannelore Daniel
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Prof. Hannelore Daniel
Prof. Daniel is head of the Department of Nutrition Physiology at TUM and co-author of the recent study. She and her team focus on the basic principles of nutrient transport in mammals on a molecular level. They also study the adaptation of metabolic processes to changes in nutrient intake and other changes.
In view of the growing number of diabetics and obese individuals, the new organoid method can help nutritional researchers develop novel diabetes therapies.
  (© TUM Technical University of Munich, AcademiaNet)

More information

Source

  • Tamara Zietek, Eva Rath, Dirk Haller und Hannelore Daniel: Intestinal organoids for assessing nutrient transport, sensing and incretin secretion, Nature Scientific Reports 19.11.2015, DOI: 10.1038/srep16831

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