PDGFRα signaling drives adipose tissue fibrosis by targeting progenitor cell plasticity.

Fibrosis is a common disease process in which profibrotic cells disturb organ function by secreting disorganized extracellular matrix (ECM). Adipose tissue fibrosis occurs during obesity and is associated with metabolic dysfunction, but how profibrotic cells originate is still being elucidated. Here, we use a developmental model to investigate perivascular cells in white adipose tissue (WAT) and their potential to cause organ fibrosis.

Retinal laser burn-induced neuropathy leads to substance P-dependent loss of ocular immune privilege.

Inflammation in the eye is tightly regulated by multiple mechanisms that together contribute to ocular immune privilege. Many studies have shown that it is very difficult to abrogate the immune privileged mechanism called anterior chamber-associated immune deviation (ACAID). Previously, we showed that retinal laser burn (RLB) to one eye abrogated immune privilege (ACAID) bilaterally for an extended period of time.

Human corneal fibrosis: an in vitro model.

Purpose: Corneal injury may ultimately lead to a scar by way of corneal fibrosis, which is characterized by the presence of myofibroblasts and improper deposition of extracellular matrix (ECM) components. TGF-beta1 is known to stimulate overproduction and deposition of ECM components. Previously, an in vitro three-dimensional (3-D) model of a corneal stroma was developed by using primary human corneal fibroblasts (HCFs) stimulated with stable vitamin C (VitC).

Growth factor regulation of corneal keratocyte differentiation and migration in compressed collagen matrices.

Purpose: To evaluate a novel 3D culture model of the corneal stroma and apply it to investigate how key wound-healing growth factors regulate the mechanics of corneal keratocyte migration.

Methods: Rabbit corneal keratocytes were seeded within collagen matrices that were compacted using external compression. Six-millimeter-diameter buttons were then incubated in media supplemented with 10% FBS, TGFbeta1, TGFbeta2, platelet-derived growth factor (PDGF), or no growth factor (control).

An experimental model for assessing fibroblast migration in 3-D collagen matrices.

The purpose of this study was to develop and test a novel culture model for studying fibroblast migration in 3-D collagen matrices. Human corneal fibroblasts were seeded within dense, randomly oriented compressed collagen matrices. A 6 mm diameter button of this cell-seeded matrix was placed in the middle of an acellular, less dense outer collagen matrix.

Matrix stiffness and serum concentration effects matrix remodelling and ECM regulatory genes of human bone marrow stem cells.

The effects of mechanical stimulation of cell-seeded collagen constructs on cell orientation, intracellular signalling and molecular responses have been widely reported. In this study we investigated in vitro the contractile responses of human bone marrow stem cells (HBMSCs) to increasing collagen gel substrate stiffness and their effect on extracellular matrix (ECM) regulatory genes. Human dermal fibroblasts (HDFs) were used as controls.

Regulation of corneal fibroblast morphology and collagen reorganization by extracellular matrix mechanical properties.

Purpose: To investigate how extracellular matrix mechanical properties influence cell and matrix patterning in three-dimensional culture.

Methods: Human corneal fibroblasts were seeded within 30 x 10 mm collagen matrices that were unconstrained (UN), fully constrained (CO) along the long axis by attaching the construct to two immobilized plastic bars, or partially constrained (PC) by allowing linear elastic displacement of one bar. After 24 hours, constructs were labeled with phalloidin and were imaged using fluorescent and reflected light (for collagen) confocal microscopy.