Fibroblasts are an essential component of the heart, as they play key roles in its structure, development and response to cardiac damage. In this context, a recent study led by the University of Barcelona presents an innovative
in vitro model that enables the precise analysis of the activation mechanisms, cellular identity and functional properties of cardiac fibroblasts. These cells are not only fundamental during the embryonic development of the heart, but also play a decisive role in the fibrosis processes associated with various cardiovascular diseases.
This breakthrough, published in the journal Disease Models and Mechanisms, represents the first in vitro model developed in transgenic mice that enables specific isolation of fibroblasts derived from the outer layer of the heart (the epicardium).
This innovative tool enables a more precise analysis of the role of these cells in cardiac fibrosis and, furthermore, paves the way for the screening and development of new therapeutic strategies for which fully effective drug treatments are still lacking.
The study is led by Professor Ofelia Martínez-Estrada, principal investigator at the UB Institute of Biomedicine (IBUB) and a member of the Celltec UB research group at the Department of Cell Biology, Physiology and Immunology at the Faculty of Biology. The first authors are Claudia Müller-Sánchez and María Gertrudis Muñiz-Banciella, also from the Celltec UB group and the IBUB. Co-authors include Professor Manuel Reina, from Celltec UB, and Professor Francesc X. Soriano, from the same research group and the UB Institute of Neurosciences (UBneuro).
Cells that play a crucial role in heart development
Over the past few decades, various transgenic mice models have been developed based on WT1 gene expression. This gene is expressed in the epicardium and in epicardium-derived cells during cardiac development, and also plays a key role in the development of the coronary vasculature.
As part of the study, the team developed a triple-transgenic mouse model that enables the tracing and characterization of epicardium-derived fibroblasts using reporter expression of WT1 gene activity.
“Epicardium-derived fibroblasts are key cells in both the formation of the embryonic heart and cardiac fibrosis,” says Professor Ofelia Martínez-Estrada, who leads research into cell biology and cardiovascular development at the UB’s Department of Cell Biology, Immunology and Physiology and the IBUB.
“Using this animal model, we have succeeded in selectively obtaining immortalized fibroblasts. The result is a valuable and versatile in vitro platform that allows us to study the activation, differentiation and plasticity of these cells, processes that are crucial in adult heart fibrosis,” say lead authors Claudia Müller-Sánchez and María Gertrudis Muñiz-Banciella, who have been selected for the “First Person” section of the journal.
Repairing the scars left by a heart attack
In addition to these findings, the team has successfully fine-tuned and optimized cell culture conditions to selectively promote the growth of specific fibroblast subpopulations, thereby enhancing the flexibility of the model presented in the article. In turn, these advances may provide a deeper understanding of the functions of these cells.
“The immortalized fibroblasts generated in this study provide a valuable means of identifying the pathways through which stimuli induce fibrosis in cardiac fibroblasts. This scientific contribution serves as a complementary tool to in vivo studies,” explain Claudia Müller-Sánchez and María Gertrudis Muñiz-Banciella.
The ability to genetically modify these cells opens up new possibilities for developing models tailored to different markers. “This breakthrough would help us better understand the cellular and molecular processes that drive fibrosis in the heart and would facilitate the development of more targeted and effective treatments,” the experts note.
“The scientific significance of this model also extends beyond studies of heart development,” they continue. “Fibroblasts that proliferate following a heart attack closely resemble to neonatal fibroblasts, and this characteristic highlights the relevance of our model, given that in adult mammals the heart has a limited capacity for regeneration.”
“Furthermore, recovery following a heart attack occurs through scar formation, in which resident fibroblasts of epicardial origin play a central role,” the authors state. “Understanding the regulatory mechanisms governing the proliferation and differentiation of cardiac fibroblasts into specific subpopulations could help develop therapeutic strategies that mitigate the effects of pathological fibrosis, while preserving the essential wound-healing processes after cardiac injury,” the researchers conclude. Reference article: Müller-Sánchez, Claudia et al. “An innovative in vitro model for studying the biology of cardiac 1 fibroblasts originating from the epicardium”. Disease Models and Mechanisms, April 2026. DOI: 10.1242/dmm.052601