A study led by the Institute for Bioengineering of Catalonia (IBEC), located at the Barcelona Science Park, has developed an innovative method to control the formation of structures similar to crypts and villi in the intestine using a contact protein imprinting technique. The research, published in the journal Nature Communications, will allow the detailed study of key processes such as cell regeneration or alterations linked to diseases such as cancer and chronic inflammatory disorders.

The methodology developed by IBEC’s Biomimetic Systems for Cell Engineering group is based on the imprinting of defined patterns of key proteins, such as Wnt3a and EphrinB1, onto a basement membrane. These proteins are essential for the organization and differentiation of the intestinal epithelial tissue. Thanks to this technique, the researchers were able to control how and where structures such as intestinal crypts and villi are formed.

Contact protein printing enables individual analysis of factors involved in the organization and function of the intestine, revealing their role in key processes such as cell proliferation and differentiation. “We have observed, for example, that Wnt3a can reduce the production of the same endogenous factor, which opens up new possibilities for manipulating these signaling pathways,” says IBEC senior researcher Jordi Comelles, associate professor at the University of Barcelona (UB) and co-author of this study.

The new approach makes it possible to control how intestinal cells are grouped, depending on the size and arrangement of protein patterns. The main objective of the study is to create a system “that more accurately reflects the conditions of the human intestinal tissue,” explains Elena Martínez Fraiz, IBEC senior researcher and UB associate professor and leader of the study. In this sense, this model enables the detailed study of key processes such as cell regeneration or alterations linked to diseases such as cancer and chronic inflammatory disorders.

On the other hand, the IBEC team used computational models to simulate the interactions between the signaling pathways, gaining a more detailed view of the processes involved in cellular organization. This breakthrough not only contributes to a better understanding of intestinal biology, but also offers new opportunities to test drugs, study diseases in a controlled environment and develop more effective treatments.

» Reference article: Larrañaga, E., Marin-Riera, M., Abad-Lázaro, A. et al. Long-range organization of intestinal 2D-crypts using exogenous Wnt3a micropatterning. Nat Commun16, 382 (2025). doi:https://doi.org/10.1038/s41467-024-55651-7

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