The ability to grow human tissue in the lab has progressed rapidly over recent years, promising a new frontier for regenerative medicine and experimental modelling of human diseases, including for early detection research. The in vitro culture of the gastrointestinal (GI) tract is particularly attractive due to the prevalence of disorders of this tissue, 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 required to form a functional tubular GI tract makes this tissue 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 different scaffold materials have been tested but there is still room for improvement.
To generate GI tracts that are representative of those in the body, Dr Linna Zhou and Dr Carlos Ruiz Puig from Professor Xin Lu’s (Ludwig Institute for Cancer Research) and Professor Hagan Bayley’s (Department of Chemistry) labs have researched the use of collagen protein as a scaffold. In their paper published in the journal Advanced Functional Materials, the researchers developed a new and simple method to construct tubular GI tracts from collagen without some of the additional steps that have been used by others previously.
Their method uses precise 3D printing of droplets containing cells and collagen, which then form into continuous tubes. Importantly, the complex tubular shape 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.
They 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 the important layered structural features found in the natural GI tract. The engineered stomach tissues were susceptible to infection with the cancer-associated bacteria Helicobacter pylori, providing a valuable early disease model.
These advanced bioengineered GI tracts therefore show great potential both for use as a disease model in biological research and for regenerative medicine. Future plans include using these engineered GI tracts to study GI cancer development and progression. Understanding more about the biology of early cancer will assist with strategies for early detection. This model will also be used to test therapeutic agents.