Bioengineering the human gut

An interdisciplinary collaboration generates an advanced model of the human gastrointestinal tract with broad applications for disease research and regenerative medicine.

The ability to grow human tissue in the lab has progressed rapidly in recent years, promising a new frontier for regenerative medicine and the experimental modelling of human diseases. Improving cultures of the gastrointestinal (GI) tract has been a high priority due to the prevalence of GI disorders, including irritable bowel disease and cancer and the need for replacement tissue for transplantation. However, the number of different cell types and the precise arrangement of cells required to form a functional tubular GI tract makes this tissue especially challenging to grow in the lab.

A common strategy for constructing GI tracts is to use a scaffold material to establish the tissue structure, which is then seeded with human cells that stick to the structure and grow. Various scaffold materials have been tested, but there is plenty of room for improvement.

To generate GI tracts that are more representative of those in the body, Linna Zhou and Carlos Ruiz Puig at Xin Lu’s Ludwig Oxford lab studied the use of collagen as a scaffold in collaboration with Hagan Bayley’s laboratory at Oxford University. In a paper published in the journal Advanced Functional Materials, the researchers describe a simpler and more efficient method to construct tubular GI tracts using the protein.

Their method uses precise 3D printing of droplets containing cells and collagen, which then form into continuous tubes. The complex tubular shape of the cultured GI tract was produced by controlling the density of the fibroblasts—cells that produce the structural framework for animal tissues—seeded at different sections of the GI tracts.

The researchers generated different types of GI tract (intestine and stomach) by seeding the collagen structures with human cells from different tissues and were able to demonstrate that their method could replicate the layered structural features found in the natural GI tract. The engineered stomach tissues were susceptible to infection with the bacteria Helicobacter pylori, providing a potentially valuable model to study cancers associated with the pathogen.

The researchers plan to use their engineered GI tracts to study GI cancer progression and test therapeutic agents.


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