Health
A new therapeutic approach to maintain the non-inflammatory stage of Crohn’s disease
The metabolism of intestinal stem cells is promoted by mitochondria, an intracellular power plant. The chronic inflammatory process inhibits cell metabolism and leads to loss of function of these stem cells.
The TUM team, in collaboration with Helmholtz Centrum Munich and the University of Paris, discovered this relationship by analyzing intestinal epithelial cells in patients with Crohn’s disease and comparing them to findings in a mouse model.
The interrelated roles of stem cells and Paneth cells
Stem cells are essential for tissue maintenance and regeneration. The intestinal stem cells in the gut are called guardians of the stem cell niche because they mix with so-called Panes cells, which are responsible for creating a local immune defense and an environment in which the stem cells can thrive.
Patients with Crohn’s disease have fewer Panes cells and, moreover, their function is limited. The research group investigated the cause of Paneth cell changes and sought to determine the importance of stem cell metabolism in this context.
In addition to the mouse study, researchers analyzed intestinal biopsies from patients with Crohn’s disease to further characterize the stem cell niche. Six months later, the patient’s intestine was re-endoscopically focused, focusing on finding signs of inflammation.
Predicting recurrence of Crohn’s disease by observing the appearance of stem cells
This study showed that microscopic changes in the stem cell niche were particularly prevalent in patients who had symptoms of recurrent inflammation after 6 months.
These changes in the stem cell niche are very early indicators of the onset of the inflammatory process. Thus, the emergence of a stem cell niche can be used to assess the probability of disease recurrence after excision of the first affected part of the small intestine. This is a good starting point for therapeutic intervention. ”
Dirk Haller, Professor of Nutrition and Immunology at TUM
Recovery of stem cell function
Paneth and stem cell changes were consistent with decreased mitochondrial function in both human patients and mouse models.
Knowing that reduced mitochondrial respiration leads to changes in the stem cell niche, researchers used dichloroacetic acid (DCA), a drug indicated to treat cancer that leads to increased mitochondrial respiration.
Alterations in DCA-induced cellular metabolism can restore intestinal stem cell function in mice suffering from inflammation, as demonstrated by intestinal organoids, organ-like structures cultured in ex vivo. I’m done.
Therapeutic approaches to prolong the non-inflammatory phase of Crohn’s disease
“These findings point to a new therapeutic approach to prolonging the non-inflammatory remission phase of Crohn’s disease,” says Eva, scientist and co-author of the TUM Life Science School of Life Sciences.・ Russ said.
The purpose of further studies is to investigate in more detail the effects of DCA in animal models and patients. So-called metabolic intervention-By targeting the metabolism of cells, the loss of stem and Paneth cell function can be prevented. Both of these maintain the gut barrier. This will prevent subsequent inflammation.
Source:
See journal:
Khaloian, S. , other (2020) Mitochondrial disorder predicts recurrence of Crohn’s disease by migrating intestinal stem cells to dysfunctional Paneth cells. Intestine. doi.org/10.1136/gutjnl-2019-319514.
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