Scientists at the Institute for Bioengineering of Catalonia (IBEC) have developed an innovative technique that enables the precise organization and differentiation of intestinal epithelial tissue. The Biomimetic Systems for Cell Engineering group at IBEC has crafted a system based on the imprinting of key proteins—such as Wnt3a and EphrinB1—onto a basement membrane. These proteins are pivotal in guiding the formation of critical intestinal structures like crypts and villi.

This cutting-edge method not only controls where and how these structures form but also allows researchers to study the individual roles of these proteins in a controlled environment. Findings from the new study were published recently in Nature Communications.

Precision in Action

"The cells we work with self-organize into compartments that replicate intestinal structures with remarkable accuracy. Using our method, based on contact printing of proteins, we control where these structures form by arranging the proteins into specific patterns, like circles or holes," explained Jordi Comelles, senior IBEC researcher, associate professor at the University of Barcelona, and co-author of the study.

This technique also provides unprecedented insight into the roles of specific proteins in processes such as cell proliferation and differentiation. "We discovered, for instance, that exogenous Wnt3a can suppress the production of its endogenous counterpart, creating new opportunities to manipulate these signaling pathways," added Comelles.

A Closer Look at Intestinal Biology

The approach reveals how the arrangement and size of Wnt3a patterns dictate how intestinal cells cluster, creating a system that more closely mimics human intestinal tissue. "This model allows us to investigate critical processes like cell regeneration and the changes associated with diseases like cancer or chronic inflammatory disorders," shared Elena Martínez Fraiz, senior IBEC researcher, associate professor at UB, and leader of the study.

By integrating computer models to simulate signaling pathway interactions, the team gained a comprehensive understanding of cellular organization processes. This breakthrough not only deepens our knowledge of gut biology but also paves the way for testing drugs, studying diseases in controlled environments, and developing more targeted treatments.

A Collaborative Effort

This research forms part of Enara Larrañaga's doctoral thesis under Martínez's guidance. The study also involved collaborations with IBEC’s Bioengineering in Reproductive Health group, the Centro de Investigación Biomédica en Red (CIBER-BBN), the European Molecular Biology Laboratory (EMBL) in Barcelona, and the Institute for Research in Biomedicine of Barcelona (IRB).

This innovation represents a leap forward in biomimetic systems, setting the stage for transformative advances in understanding and treating gastrointestinal diseases.