October 3, 2022

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The most complicated stomach organs so far are born

The most complicated stomach organs so far are born



Cell Sub-Journal: The most complicated stomach organs so far are born.

In 2009, Hans Clevers and others at Hubrecht Research Institute in the Netherlands used adult stem cells from the intestines of mice to cultivate the first intestinal organoids, ushering in the era of organoid research.

He also won the 2013 Scientific Breakthrough Award (Breakthrough Prize), Hans Clevers established organ class technology incubator company Hubrecht Organoid Technology, and successfully hatched a number of organ class research company.

In 2019, Hans Clevers, as a co-founder, founded Xilis, an organoid research company. The company received US$70 million in financing this year and received widespread attention.

Since 2009, research results in the field of organoids have continued, and many new types of organoids 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 research paper titled: Functional human gastrointestinal organoids can be engineered from three primary germ layers derived separately from pluripotent stem cells in Cell Stem Cell .

This research has developed the most complicated stomach organ so far , which has unique glands and nerve cells that can control smooth muscle contraction . The research team said that this is an important step forward for regenerative medicine.

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.

The most complicated stomach organs so far are born

So far, most organoids developed can form 3D structures involving multiple cell types. In laboratory petri dishes, these tiny organoids perform functions, providing new opportunities for the research of diseases and the development of treatments.

But they often lack the many cell types needed to produce full-scale functional organs, such as the 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 from the three main germ layers of human pluripotent stem cells (HPSC)-enteric 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 enteric neurons that control the contraction of engineered gastric antrum tissue.

The most complicated stomach organs so far are born

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

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

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

Although the complex gastric organoid in this new study does not yet contain all gastric cell types, it still represents a leap forward.

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

After being cultured for about 30 days, the research team transplanted them into mice through microsurgery, providing blood and biological space for a period of time. To allow it to continue to grow.

These gastric organoids have increased a thousand times in volume in mice, forming microscopic organs that are visible to the naked eye, rather than tiny cell spheres in a petri dish.

When viewed under a confocal microscope, different cell types are stained and emit different colors of light, and these organoids exude rainbow-like complexity.

In fact, these organoids are very similar to naturally-growing human tissues at similar developmental stages.

These organoids even begin to develop Brenner’s glands, which secrete an alkaline mucus that protects the duodenum from gastric acid when the contents of the stomach flow out.

The research team also found that in order to generate gastric tissue with appropriate complexity and function, all these individual components are needed, each of which helps guide the correct formation of other components.

For example, if nerves are not added during the assembly process, stomach glands and muscles will not form properly.

The most complicated stomach organs so far are born

The research team has already begun working to extend this study to the mouse outside the research team believes the animal as a host to cultured cells derived from human organ class, the class will be transplanted organs and tissues to the human patient final method.

However, the clinical use of such organoid transplantation needs to comply with GMP standards, which may limit the possibility of long-term production of organoids by animals as a host.

Therefore, the research team is developing methods to keep organoids growing without the need for a host animal.

The research team said that although there is still a long way to go before sending out organoids suitable for human transplantation, great progress has been made now.

The research team’s goal is to transplant organoids to patients by 2030 .

Paper link:
https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(21)00435-5

The most complicated stomach organs so far are born

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