Stem cells are unique for their use in developing various types of cells. They are also used to create organoids or tissue cell structures that replicate organs. French scientists have developed a new way to engineer mini-intestines with fewer restrictions than other methods of making organoids.
A team from Ecole Polytechnique Fédérale de Lausanne used tissue engineering and self-organization properties of intestinal stem cells to create mini-gut tubes. Their findings were published in the journal Nature.
Ever since the development of organoids in the early 1900s, there have been many scientific breakthroughs such as drug developments and testing. Human stem cells can be manipulated to create live tissue that can replicate parts of organs such as the heart and lungs. Scientists are aiming to use organoids to replace damaged tissue or new organs for transplants in the future.
Creating a Mini Intestine
For the stem cells to organize themselves into an intestinal organoid, the team used a laser to sculpt the mini-gut tubes within a hydrogel. Hydrogels are a network of proteins that form a soft gel that encases the stem cells. As the stem cells grow, the hydrogel acts as a mold for the organoid's final shape.
It only took a few hours for the stem cells to spread within the hydrogel to form a mini-intestine. What surprised the team was how stem cells can self-organize to form a functional organoid.
Matthias Lütolf said, "It looks like the geometry of the hydrogel scaffold, with its crypt-shaped cavities, directly influences the behavior of the stem cells so that they are maintained in the cavities and differentiate in the areas outside, just like in the native tissue." The cells did not simply multiply to fill the shape of the hydrogel, but also produced the various cell types found in a real intestine and included specialized cells atypical of organoids.
Previous methods of developing organoids resulted in three-dimensional structures that have a limited size and lifespan, which limits scientists from conducting experiments. After inducing intestinal stem cells to form mini-intestines, the organoids were attached to an external pumping system.
READ: Scientists Use 3D Printers to Make Miniature Organs for Testing Potential COVID-19 Drugs
Multiple Intestine Functions
The bioengineered tubes became perfusable, similar to blood flow in regular intestines. As a result, the mini-intestines had a prolonged lifespan for several weeks as the pump continuously removed dead cells. Also, the extended lifespan enabled "the tubes to be colonized with microorganisms for modeling host-microorganism interactions," wrote the authors.
Adding the "microfluidic system allowed us to efficiently perfuse these mini-guts and establish a long-lived homeostatic organoid system in which cell birth and death are balanced," said Mike Nikolaev. The team was also able to demonstrate the various functions of a normal gut in the mini-organoid such as recovery from severe tissue damage through cell regeneration.
Moreover, the mini-intestine could also mimic the inflammatory processes. Since the mini-gut's lifespan was long enough to host microorganisms, the team observed interactions between the organoids and microbes in the same way that real intestines host gut bacteria.
"Tissue engineering can be used to control organoid development and build next-gen organoids with high physiological relevance, opening up exciting perspectives," said Lütolf, for various fields such as regenerative medicine, drug developments, and disease modeling.
READ: Scientists Explored the Use of 'Organoids' For a More Accurate Cancer Therapies to Treat Tumors
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