3D Cell Migration Studies for Chemotaxis on Microfluidic-Based Chips: A Comparison between Cardiac and Dermal Fibroblasts

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.

Doxorubicin induces trans-differentiation and MMP1 expression in cardiac fibroblasts via cell death-independent pathways

“…Little is known about the difference between cardiac fibroblasts and dermal fibroblasts. Pérez-Rodríguez et al observed that their cell migration abilities in response to cytokines are distinct [29]. Although several reports have demonstrated that trans-differentiation and MMP1 expression in dermal fibroblasts is associated with dermal wound healing and fibrosis, we revealed that the response of these cells to DOX is less than that of CFs.…”

Confined Cell Migration and Asymmetric Hydraulic Environments to Evaluate the Metastatic Potential of Cancer Cells

“…Collagen gels of 2.5 mg/ml concentration and pH 7.4 were created by mixing collagen type I (BD Bioscience), NaOH, Dulbecco's phosphate buffered saline, DPBS (Thermo Fisher), and culture medium with suspended cells (after trypsinization and centrifugation). MCF-7 and MDA-MB-231 cells were mixed with gel solutions at a final concentration of 2×10 5 cells/ml and pipetted into the gel cavities of the microdevice, as in previous reports [20], [42]- [46].…”

Multiscale Coupling of an Agent-Based Model of Tissue Fibrosis and a Logic-Based Model of Intracellular Signaling

“…Under normal conditions, fibroblasts migrate at a speed of ∼10 µm/h, but this can vary significantly in the presence of growth factors and cytokines (Ware et al, 1998;Pérez-Rodríguez et al, 2018). As noted above, individual grid spaces are 10 × 10 µm, so the baseline migration speed was set at 1 grid space per hour.…”