Researchers from the University of Barcelona announced on Apr. 15 the development of an innovative in vitro model that allows for precise analysis of cardiac fibroblasts, cells essential to heart structure and response to damage. The study, published in Disease Models and Mechanisms, introduces the first in vitro model using transgenic mice to specifically isolate fibroblasts derived from the epicardium, the outer layer of the heart.
This advancement is significant because cardiac fibroblasts are crucial not only during embryonic development but also play a key role in fibrosis processes linked to cardiovascular diseases. The new tool enables more detailed examination of these cells' functions and could aid in screening and developing therapies for conditions where effective treatments are currently lacking.
The research was led by Professor Ofelia Martínez-Estrada at the UB Institute of Biomedicine (IBUB), with first authors Claudia Müller-Sánchez and María Gertrudis Muñiz-Banciella from Celltec UB group. Other contributors include Professors Manuel Reina and Francesc X. Soriano.
The team developed a triple-transgenic mouse model that uses WT1 gene activity as a reporter to trace epicardium-derived fibroblasts. "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 Müller-Sánchez and Muñiz-Banciella.
The researchers also optimized cell culture conditions to promote specific subpopulations' growth, which may lead to better understanding their roles. "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 Müller-Sánchez and Muñiz-Banciella.
According to the authors, genetic modification possibilities open doors for tailored models targeting 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." They add that their work is relevant beyond developmental studies since post-heart attack proliferating fibroblasts resemble neonatal ones—a factor important given limited regeneration capacity in adult hearts.
"Furthermore, recovery following a heart attack occurs through scar formation, in which resident fibroblasts of epicardial origin play a central role," they state. "Understanding the regulatory mechanisms governing proliferation and differentiation... could help develop therapeutic strategies that mitigate pathological fibrosis while preserving essential wound-healing processes after cardiac injury," conclude Müller-Sánchez and Muñiz-Banciella.
