The human intestine It is made up of more than 40 m2 of fabric, with a multitude of folds on its internal surface that resemble valleys and mountain peaks, to achieve, among other objectives, increase the absorption of nutrients. This organ has the particularity of being in constant renewal, which implies that approximately every 5 days all the cells of its inner wall are renewed to ensure proper intestinal function.
Until now it was known that this renewal was possible thanks to the stem cells that are protected in the so-called crypts or valleys intestinal, and that give rise to new differentiated cells. However, the process that leads to the concave shape of the crypts and the migration of new cells into the peaks intestinal, until now it was unknown.
Experiments with laboratory organoids or mini-intestines and 3D models have made it possible to decipher how the intestinal valleys fold and the migration movement of cells towards the summits occurs.
Now scientists from Institute of Bioengineering of Catalonia (IBEC), in collaboration with others from the Institute for Biomedical Research (IRB), the Universities of Barcelona and Polytechnic of Catalonia and the Curie Institute in Paris, have deciphered the mechanism by which crypts adopt and maintain their concave shape, and how movement occurs of migration of the cells towards the tops, without the intestine losing its characteristic folds.
To do the job they have combined computer modeling with experiments with organoids intestinal cells from mice, and the results, published in the journal Nature Cell Biology, show that this process is possible thanks to the mechanical forces exerted by the cells.
Mouse Cells Mini Intestines
The authors have used mouse stem cells and combined bioengineering and mechanobiology techniques to develop mini intestines, organoids that reproduce the three-dimensional structure of valleys and peaks recapitulating the functions of tissue in vivo.
Microscopy technologies, developed in the same group, have made it possible for the first time to carry out high resolution experiments and obtain 3D maps showing the forces exerted by each cell.
Furthermore, with this in vitro model, the researchers have shown that the movement of the new cells to the top is also controlled by mechanical forces exerted by the cells themselves. Specifically, by the cytoskeleton, a network of filaments that determines and maintains cell shape.
“With this system we have discovered that the crypt is concave because the cells have more tension on their upper surface than on the lower one, which makes them adopt a conical shape. When this occurs in several cells next to each other, the result is that the tissue folds, giving rise to a relief of valleys and peaks ”, explain the co-author Carlos Pérez-González.
For its part, another of the authors, Gerardo Ceada, highlights: “Contrary to what was believed until now, we have been able to determine that it is not the cells of the intestinal crypt that push the new ones up, but rather the cells at the top that pull the new ones up. , something like a mountaineer who helps another to climb by pulling him “.
Applications to better understand and treat diseases
The new model of the mini-intestine will allow the study, in reproducible and real conditions, of diseases such as cancer, celiac disease, or colitis, in which there is a lack of control in the multiplication of stem cells or a destructuring of the folds.
On the other hand, intestinal organoids can also be manufactured with human cells and used for the development of new drugs or in the study of the intestinal microbiota.
In addition to granting a grant to Ceada to carry out his doctorate at IBEC, the ”la Caixa” Foundation has supported an important part of this study within the framework of the program CaixaResearch.
Co-authors Xavier Trepat (ICREA Research Professor at IBEC), Gerardo Ceada (awarded a CaixaResearch scholarship to carry out his doctorate at IBEC) and Marino Arroyo (UPC professor, IBEC associate researcher and member of CIMNE, in charge of modeling By computer). / IBEC
C. Pérez-González, G. Ceada, F. Greco, M. Matejčić, M. Gómez-González, N. Castro, A. Menendez, S. Kale, D. Krndija, AG Clark, V. Ram Gannavarapu, A. Álvarez-Varela, P. Roca-Cusachs, E. Batlle, D. Matic Vignjevic, M. Arroyo and X. Trepat. “Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration”. Nature Cell Biology, 2021.
Rights: Creative Commons.