Map of intestinal cells to help the chronically ill

Thursday 26 Sep 19

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Peter Bjørnlund Jørgensen
Postdoc
DTU Health Tech
+4535 88 68 15

Contact

William Winston Agace
Groupleader, Professor
DTU Health Tech
+4535 88 68 99

Chronical inflammatory intestinal diseases (IBD)

Crohn’s disease
Crohn’s disease may impact all parts of the intestinal system from the pharynx to the rectum. Most frequently however in the area between the small and the large intestines. The inflamed area becomes red, swollen and painful and may possibly bleed. It is characteristic for this disease that it may cause so-called inflamed lumps (granulomas) in the intestinal wall, only visible through a microscope.

The inflammation may also cause scar tissue (fibrosis). Both the inflamed lumps and the scar tissue may lead to constriction in parts of the intestines. The affected areas in the intestines are thereby unable to uphold their regular functions with regard to absorbing nourishment. This may cause diarrhoea.

Ulcerative colitis
This disease often affects the rectum and the nether parts of the large intestine (colon). The disease may however attack the entire large intestine. The inflammation is first and foremost situated in the mucous membrane of the intestines where wounds appear. The inflammation has the effect that the large intestine will seek to empty itself more regularly.

Ulceration in the mucous membrane leads to bleeding and produces pus and slime. This may cause bloody diarrhoea.  Like Crohn’s disease, ulcerative colitis may be difficult to diagnose because several intestinal diseases have similar symptoms in the early stages.

Source: Patienthåndbogen, Sundhed.dk

Better knowledge about our intestinal cells can provide better treatment for diseases such as Crohn’s Disease or Ulcerative colitis in the future. At DTU Health Tech, PhD student Peter Jørgensen has just defended his thesis where he has contributed to mapping of the cells in our intestines.

More than 70,000 Danes suffer from serious, inflammatory bowel diseases such as Crohn’s Disease and Ulcerative colitis. At present, it is unknown exactly which factors cause this lamentable development, but the number of people affected is on the rise particularly in the western world.

 

If we come to an understanding of what initiates and causes the reoccurrence of the diseases to the intestine in IBD (Inflammatory bowel disease), we will be better equipped to prevent and treat these diseases. To do that, it is important that we further understand the cellular architecture of the intestine.

 

The intestine is very complex
The intestine in a human adult is almost 8 meters long and has an absorbing surface of about 30-40 m2. The intestine is thereby the organ with the largest surface in the body. The entire intestine, from pharynx to rectum is constantly exposed to large amounts of “foreign material” for example in the form of nourishment and the millions of bacteria and microorganisms, which inhabit the intestine. A breakdown of the intestinal wall may lead to a local, chronic inflammation and scar tissue formation, which consequently may cause constrictions.

 

In his PhD project, Peter Jørgensen analysed human stromal cells in collaboration with researchers at Herlev hospital. He explains that the inside of the small intestine is covered with small finger-like projections similar to the surface of a sea anemone – the so-called “villi”. The surface of the “villi” consists of various epithelial cells, which are well described. But just beneath this cell layer, there is a number of supporting cells, which have not received nearly as much attention – the stromal cells”.

 

“Some types of stromal cells actually contribute to suppress the immune system. This is an important function, which we have only recently become aware of. Even though we do not know much about the intestinal stromal cells, we assume that similar processes occur in the intestine as in the rest of the body”, Peter Jørgensen says. Stromal cells do not move around in the same manner as immune cells and they are not renewed at the same speed as epithelial cells, which is exactly why they are interesting in relation to their communication with the immune system. 

 

Importance of restraining the intestinal immune system
Tolerating harmless elements, such as food, and at the same time remaining responsive to dangerous microorganisms is probably one of the most important functions of the intestinal immune system. However, triggers such as genetics and other unknown factors can alter this balance and initiate inflammation, which may become chronic.

 

Previously surgery was the only treatment for inflammatory bowel diseases. Even though biological treatment can help patients today to moderate the immune system and thereby suppress inflammation, the disease may return in the same area as before, and many patients actually become unresponsive to the treatments and end up undergoing surgery anyway. So tackling the issues of chronicity and disease (re)initiation by restraining the intestinal immune system is very important. This is where Peter Jørgensen’s results will have an impact.

 

From basic research to applicable knowledge
In short, using advanced methods of analysis, researchers apply various markers to the stromal cells to recognize and separate the different types of cells. E.g. immune restraining cells, immune alarming cells etc. An awareness of the differences in the immune response and the positioning of the cells means that we may learn more about why some diseases only occur in some places in the intestines and not others.

 

No such map exists at present and the literature has a tendency to mix-up the different types of cells. Therefore, Peter Jørgensen believes that these results can form a good platform for other research groups, who can use the new data and continue their research on a much better foundation.

 

 

The illustration shows an enlargement of the intestinal wall and a villus (about 1 mm). The stem cells are placed in the nether part of the villi and develop into epithelium cells while they move upwards. When the epithelium cells reach the top of the villi they die and are released. The whole process only takes 5-7 days. Under normal circumstances, the stromal cells stay in the same place during the entire process and engage in close communication with the immune cells (here, all seven types of stromal cells are shown as yellow cells). Illustration by Nanna Bild.


Histology section of the wall of the small intestine.

 

Peter Jørgensen’s work is part of the 5-year RIMMI project, funded by the Lundbeck Foundation. You can read about the RIMMI project here.