Objective: Fibrotic diseases may be described as a disease of the extracellular matrix, where the balance between matrix formation and degradation has been shifted leading to an accumulation of matrix. Currently a fit for purpose model and readily available approach are adapted when doing cell cultures, which may not reflect physiology and pathophysiology optimally. The aim of this review is to draw special attention to the similarities and differences of current state of the art in vitro and ex vivo models, with special focus on the proteins, cell-cell interactions, and correct matrix composition, which may be a better representative of in vivo conditions in a disease where the extracellular matrix is the central player.

Methods: We reviewed current literature with emphasis on the role of the extracellular matrix in health and disease, different fibrotic disease models, and highlighting the importance of this when looking at translational science.

Conclusion: To further our fibrotic research one paramount problem is to fundamentally understand the core of the disease, the production and degradation of the extracellular matrix. For a surprisingly long time the ECM has been underestimated until recently, with the discovery that the ECM may control cell phenotype through cell-matrix interactions. This highlights the need of a native ECM when investigating pathways and response to potential therapy. Clearly, both in vitro and in vivo models provide fit to purpose benefits, but in particular for the fibrosis field we may ask, do single cell cultures in monolayers recapitulate the complicated ECM environment controlling cell fate?

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