The term ‘gastrointestinal (GI) diseases’ covers a wide range of conditions affecting all parts of the digestive system. These conditions affect millions of people worldwide, creating a significant burden on healthcare systems. This wide spectrum of GI diseases means that a large amount of research is performed to understand their development and generate treatments, with much of it currently conducted using animals including mice, rats, guinea pigs, zebrafish, rabbits, dogs, pigs and monkeys. These methods have limitations due differences in the anatomy, gene expression and immune system between animals and humans, and often include cruel surgical or stress-induced approaches.
To replace animals used in GI disease with human-focused methods, Dr Driton Vllasaliu at King’s College London, worked on developing organoids (simplified mini versions of human organs), which can be grown in the lab. Organoids are useful for understanding how cells behave, identifying changes that lead to disease and for testing new drugs and treatments. Additionally, organoids have a huge advantage over animal experimentation, as they can be developed from human or patient-derived cells that better reflect what happens in the patient’s body.
Using pilot funding from Animal Free Research UK, Dr Vllasaliu, developed an improved version of a human intestine organoid. The motivation for this research was one of the main limitations of gut organoids, relating to the structure of the intestine itself, which is shaped like a long tube. The inner wall of the intestine, known as the luminal side, is important for the absorption of food and drugs, but is also one of the main areas involved in disease development. Current intestinal wall models, are limited in their usefulness because they are grown as a 3D structure with the important luminal side cells facing inside, making these cells inaccessible to researchers.
Dr Vllasaliu developed a new way to grow the luminal intestine cells as a thin 2D layer, meaning the luminal cells are easily accessible for a range of research including drug development, drug safety testing and assessing nutritional absorption.
Initial testing of the model was completed, and future work will focus on further testing to understand how this technology can continue to be improved and used more widely. This work is a significant advancement in animal-free technology and represents an important step forward in the replacement of animal experiments in the field of GI disease research.