iChip · Intestine-on-a-chip for investigating microbioal-epithelail interaction
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-01-01 → 2021-02-12
- EU contribution
- €212,195
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Intestine-on-a-chip for investigating microbioal-epithelail interaction
This project aimed to develop a microfluidic device wherein intestinal stem cells culture be culture in a more in vivo-like environment than the current state of the art culture techniques. The closer the culture environment can mimic the body the better ques the cells will receive to preserve their phenotype as like as possible to how the cells function in the human body, or the better their differentiation can be guided into a functional mature cell. The cells of the human body are naturally not receding in a static microenvironment where things stay the same, rather are they placed in a dynamic environment where they are constantly subjected to different outside stimuli, both in the form of signals from other cells or from mechanical stimuli as a result of body or muscle movement or internal fluid movement. By realizing a body like culture environment for the cells the scientific results obtained from cell biology studies will be more relevant and likely the cells will respond more similar to how they would respond in the body, including results from drug trial for example.
Data: CORDIS, © European Union
Project objective
The small intestine forms a barrier that protects us against the outer world. Here commensal bacteria are tolerated while pathogens are effectively fought off. Occasionally, however, pathogenic bacteria colonize the intestine causing different diseases, which constitute a huge burden worldwide. The ability to study interactions of pathogenic bacteria with the intestine will provide new insights into the disease mechanisms, and new therapeutic targets and ways to prevent disease occurrence. Current animal and 2D models based on tumor cell lines both have shortcomings as they react differently to pathogenic bacteria when compared to healthy human tissues.Primary intestinal epithelial cells can now be cultured as intestinal mini-guts, 3D mini organs. This has partly overcome some of these shortcomings with mouse models and tumor cell lines. These mini-guts are, however, challenged topologically as the intestinal lumen is facing towards the inside of the structures. This makes it difficult to access the luminal surface and study microbial interactions with the epithelium. Furthermore, the static culture conditions do not mimic the in vivo conditions closely enough.I will use microfluidics and microengineering to develop an intestine-on-a-chip device based on primary human intestinal epithelial cells expanded as mini-guts but assayed on mimics of the natural villi structures found in the small intestine. Additionally, the model will allow the fluidic (sheer stress) and mechanic (peristalsis) microenvironment to be closely controlled in order to generate in vivo-like conditions. This is important to study as e.g. Crohn’s disease, that induces suppressed peristalsis, is associated with intestinal inflammation and bacterial overgrowth. Altogether, this intestine-on-a-chip device will go beyond state-of-the-art and for the first time give causality to the number of correlative studies reporting on how commensal and pathogenic gut bacteria affect the human physiology.
Original text from CORDIS.
Participants
- KOBENHAVNS UNIVERSITET · KOBENHAVNCoordinatorDenmark
Links
Data: CORDIS, © European Union