Intestine-on-a-chip for investigating microbioal-epithelail interaction

Informations projet

iChip

N° de convention de subvention: 746270

DOI

10.3030/746270

Projet clôturé

Date de signature de la CE 14 Mars 2017

Date de début 1 Janvier 2018

Date de fin 12 Février 2021

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 212 194,80

Contribution de l’UE

€ 212 194,80

Coordonné par

KOBENHAVNS UNIVERSITET
Denmark

Periodic Reporting for period 1 - iChip (Intestine-on-a-chip for investigating microbioal-epithelail interaction)

Période du rapport: 2018-01-01 au 2019-12-31

Résumé du contexte et des objectifs généraux du projet

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.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

This project aimed to study the small intestine, and two important features of the small intestine dynamic environment that the intestinal epithelial cells are subjected to are a flow or a progression of food matter down the intestine, and the peristalsis, or the muscular motion of the intestine that results in food matter moving from the stomach towards the large intestine.

To realize a dynamic culture environment for the intestinal epithelial cells a small microfluidic device was developed (Figure 1). The device allowed for a fluid to be flown above the cultured cells to simulate this aspect of the small intestine. Furthermore, the device also allowed for mechanical stretching of the cells in a similar way as they would be stretched by the natural smooth muscle movements of the digesting intestine.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The impacts of this device are many. First the development of these more body-like culture models will result in the reduction of the use of animals in research. This will of course spare animal lives but also likely have the possibility to provide better data, as animals not always will respond as humans. This has several implications, first drugs that would potentially have been suitable for humans are discarded during the development process as they did not have the anticipated effect in an animal model, resulting in lots of resources wasted; or harmful substances could be cleared for human use as they have falsely been deemed safe, because they were not harmful to the animal. Better culture models could thus result in better use of resources as well as more safe drugs.

This model also provides them means to study biological processes that is not currently possible in current culture models or in animal models. In this model bacterial-intestinal interactions could for example be studied. This is not currently possible under static culture conditions due to the bacteria entirely taking over and over growing the cell culture, nor in the body as it is of course not possible to see these processes when they take place inside of the body.

The developed device will thus be interesting both for other researchers and for commercial companies. By this it will have a indirect impact on the general public through advancing the research results and general knowledge and through use during development of for example more advanced and better suited drugs.

Figure 1. Single intestinal epithelial cells from organoids could be cultured inside the microfluidi