IN VITRO three-dimensional (3D) cell systems are the subject of intense research, with the aim of one day replacing existing animal models. Now, a stem cell-derived model could enable in vitro investigation of inflammatory bowel disease and host-microbe-pathogen interactions. Success of an in vitro model is dependent on how effectively it mimics essential organ functions and the organ cellular environment. Researchers from Tufts University, Medford, Massachusetts, USA, cultivated human stem cell-derived small intestine-like ‘enteroids’ using a 3D silk scaffold. The system was assessed to conclude how closely the function and appearance mimicked the small intestine environment in vivo.
The research team, led by Prof Ying Chen and Prof David Kaplan, found the cells in the model had successfully differentiated into a mature epithelium layer, which was composed of four differentiated major intestinal cell types: enterocytes, goblet cells, Paneth cells, and enteroendocrine cells The production of these cells was key to producing a physiologically relevant system. Further to this, the cells displayed typical small intestine characteristics, such as tight junctions, polarised microvilli, low oxygen tension in the lumen, and secretion of digestive enzymes.
The system was also challenged with Escherichia coli infection and a significant antibacterial response was observed, in addition to an upregulation of genes associated with the innate immune response. Importantly, many of these genes are activated in humans with inflammatory bowel disease, implicating the potential application of the 3D stem cell-derived epithelium for the in vitro study of host-microbe-pathogen interplay, inflammatory bowel disease pathogenesis, and antibiotic resistance.
Although the model is a simplified representation when compared to the small intestine and its environment, there is a need for functional in vitro 3D human intestine models to bridge conventional cell culture studies and human trials. Lastly, as the small intestine enteroids are derived from native intestine tissues donated by individual patients, this produces a system capable of studying patient-specific disease mechanisms and therapeutic responses.
