Abstract
Fibroblast migration to damaged zones in different tissues is crucial to regenerate and recuperate their functional activity. However, fibroblast migration patterns have hardly been studied in disease terms. Here, we study this fundamental process in dermal and cardiac fibroblasts by means of microfluidic-based experiments, which simulate a three-dimensional matrix in which fibroblasts are found in physiological conditions. Cardiac fibroblasts show a higher mean and effective speed, as well as greater contractile force, in comparison to dermal fibroblasts. In addition, we generate chemical gradients to study fibroblast response to platelet derived growth factor (PDGF) and transforming growth factor beta (TGF-β) gradients. Dermal fibroblasts were attracted to PDGF, whereas cardiac fibroblasts are not. Notwithstanding, cardiac fibroblasts increased their mean and effective velocity in the presence of TGF-β. Therefore, given that we observe that the application of these growth factors does not modify fibroblasts’ morphology, these alterations in the migration patterns may be due to an intracellular regulation.
Highlights
Fibroblasts are the most abundant cells in connective tissue and are responsible for secreting extracellular matrix, which is rich in collagen, to give tissue consistency
Some of these signalling molecules involved in wound healing, both in epithelium and in cardiac tissue, are platelet derived growth factor (PDGF) and transforming growth factor beta (TGF-β) [5]
The PDGF family is a multifunctional group of proteins involved in a multitude of physiological functions, among which their necessary implication for the division of fibroblasts, especially myofibroblasts, and their contribution to the maintenance of connective tissue stands out
Summary
Fibroblasts are the most abundant cells in connective tissue and are responsible for secreting extracellular matrix, which is rich in collagen, to give tissue consistency. Myofibroblasts die by apoptosis [4] Some of these signalling molecules involved in wound healing, both in epithelium and in cardiac tissue, are platelet derived growth factor (PDGF) and transforming growth factor beta (TGF-β) [5]. TGF-β belongs to a family with three important isoforms, all of which are present in wound healing, which are secreted as inactive precursors that must be activated by proteolytic cutting and dimerization, allowing it to be attached to its receptors This union activates pathways aimed at blocking the cell cycle or activating an alternative differentiation program [7]. We used microfluidic devices to simulate PDGF and TGF-β gradients, and analyse the 3D migration patterns of dermal and cardiac fibroblasts under these gradients
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