The human intestine is made up of over 40 square meters of tissue, with a multitude of folds on its inner surface that resemble valleys and mountain peaks to increase nutrient absorption. The intestine also has the unique characteristic of being in a continuous state of self-renewal. This means that about every 5 days, all the cells in its inner walls are renewed to ensure proper bowel function. Until now, scientists knew that this renewal could be done thanks to stem cells, which are protected in the so-called intestinal crypts, and which give rise to new differentiated cells. However, the process that leads to the concave shape of the crypts and the migration of new cells to the intestinal peaks was unknown.
From now on, an international team led by Xavier Trepat, ICREA research professor and group leader at the Institute of Bioengineering of Catalonia (IBEC), in collaboration with the IRB, researchers from UB and UPC universities in Barcelona, and of the Institut Curie in Paris, deciphered the mechanisms leading crypts to adopt and retain their concave shape, and how the movement of cells migrating towards the summits occurs, without the intestine losing its characteristic folded shape. The study, published in the prestigious journal Natural cell biology, associated computer modeling, led by Marino Arroyo, professor at UPC, associate researcher at IBEC and member of CIMNE, with experiments with intestinal organoids from mouse cells, and shows that this process is possible thanks to mechanical forces exerted by cells. An important part of this study was supported by the “la Caixa” Foundation within the framework of the CaixaResearch program. The entity also awarded a scholarship to the first co-author, Gerardo Ceada, to complete his doctorate at IBEC.
Forces determine and control the shape of the intestine and the movement of cells
Using mouse stem cells and bioengineering and mechanobiological techniques, the researchers developed mini-intestines, organoids that resemble the three-dimensional structure of peaks and valleys, recapitulating tissue functions in vivo. Using microscopy technologies developed by the same group, the researchers performed high-resolution experiments for the first time that allowed them to obtain 3D maps showing the forces exerted by each cell.
Moreover, with this in vitro model, scientists have shown that the movement of new cells towards the peak is also controlled by mechanical forces exerted by the cells themselves, more precisely by the cytoskeleton, a network of filaments that determines and maintains cellular form.
“Contrary to what has been believed until now, we were able to determine that it is not the cells of the intestinal crypt that push the news upwards, but that it is the peak cells that pull the news upwards. high, like a climber who helps another climber by pulling him “, explains Gerardo Ceada of IBEC
“With this system, we found that the crypt is concave because the alveoli have more tension on their top surface than on the bottom, causing them to assume a conical shape. When this happens in multiple alveoli side by side, the the result is that the fabric folds, giving rise to a pattern of peaks and valleys, ”adds Carlos Perez-Gonzalez (IBEC and Institut Curie).
The new mini-intestine model will allow further studies of diseases such as cancer, celiac disease or colitis to be conducted under reproducible and real conditions, in which there is an uncontrolled proliferation of stem cells or a destructuring of the folds . In addition, intestinal organoids can be made with human cells and used for the development of new drugs or for the study of the gut microbiota.
X. Trepat is a member of the Center for networking biomedical research in bioengineering, biomaterials and nanomedicine (CIBER-BBN), and professor-researcher at the Catalan Institution for Research and Advanced Studies (ICREA).
The Institute of Bioengineering of Catalonia (IBEC) is a CERCA center, it has been twice named “Severo Ochoa Center of Excellence” and received the TECNIO label as technology developer and facilitator for companies. IBEC is a member of the Barcelona Institute of Science and Technology (BIST) and conducts multidisciplinary research of excellence at the frontier between engineering and life sciences to generate knowledge, integrating fields such as nanomedicine, biophysics, biotechnology, tissue engineering and information technology applications. in the domain of health. IBEC was created in 2005 by the Catalan government, the University of Barcelona (UB) and the Polytechnic University of Catalonia (UPC).
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