"Cell Stem Cell" so far the most complicated stomach organ was born, and human transplantation will be realized within 10 years!

He also won the 2013 Science Breakthrough Award.

In 2019, Hans Clevers founded the organoid research company Xilis as a co-founder

Since 2009, research results in the field of organoids have continued to emerge, and many new and more complex organoids have continued to emerge, bringing more powerful tools to the fields of new drug development, precision treatment, and regenerative medicine

On December 1, 2021, researchers from the Cincinnati Children’s Medical Center in the United States published a titled "Three primary germ layers isolated from pluripotent stem cells can construct functional human gastrointestinal organoids" in the journal Cell Stem Cell.

This research developed the most complex stomach organ to date, which has unique glands and nerve cells that can control smooth muscle contraction

This study also shows that complex organoids can be cultivated from human pluripotent stem cells, and this method can also be used to construct complex versions of other types of organoids

So far, most organoids can form three-dimensional structures containing multiple cell types

But they often lack the many cell types needed to produce a fully functional organ, such as key nerve fibers, internal blood vessels, or other key ducts and glands needed to connect the organ to other systems in the body

The research developed a method for organ assembly, starting with the three main germ layers of human pluripotent stem cells (HPSC)-intestinal glial cells, mesenchymal cells, and epithelial precursor cells

From these three cell types, gastric tissue containing acid-producing glands is produced, surrounded by a smooth muscle layer, which contains functional intestinal neurons that control the contraction of engineered gastric antrum tissue

Using this experimental system, the research team found that human enteric neural crest cells (ENCCs) promote the interstitial development of gastric antrum organoids and gland morphogenesis

In addition, ENCC can directly act on the foregut and promote the fate of the hindgut, thereby producing organoids with the Brunner gland phenotype

Therefore, the germ layer components isolated from pluripotent stem cells can be used in tissue engineering to generate complex human organoids

Although the complex gastric organoids in this new study do not yet contain all gastric cell types, it is still a leap forward

More importantly, these miniature human stomach organoids are not limited to a thin layer in a petri dish

After more than 30 days of culture, the research team transplanted it into mice through microsurgery, and provided blood and biological space for a period of time

These gastric organoids increased a thousand-fold in volume in mice, forming microscopic organs visible to the naked eye instead of tiny cell spheres in a petri dish
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When viewed under a confocal microscope, different types of cells are stained and emit different colors of light, and these organs exude rainbow-like complexity
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In fact, these organoids are very similar to naturally-growing human tissues at similar developmental stages
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These organoids even begin to develop Brenner glands, which secrete alkaline mucus to protect the duodenum from gastric acid
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The research team also found that in order to generate gastric tissue with appropriate complexity and function, all these individual components are necessary, and each component helps guide the correct formation of other components
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For example, if nerves are not added during the assembly process, stomach glands and muscles cannot form normally
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The research team has begun to extend this research beyond mice.
The research team believes that using animals as a host to culture cells extracted from human organs will eventually transplant organs and tissues into human patients
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However, the clinical application of this type of organ transplantation needs to comply with GMP standards, which may limit the possibility of long-term production of organoids by animals as a host
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Therefore, the research team is developing methods to maintain the growth of organoids without the need for a host animal
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The research team said that although there is still a long way to go before organoids suitable for human transplantation can be produced, great progress has now been made
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The research team’s goal is to transplant organoids into patients by 2030
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