CC chemokine ligand 20 (CCL20) positively regulates collagen type I production in 3D skin equivalent tissues.

Chemokines are a group of small proteins that induce chemoattraction and inflammation and contribute to the differentiation and homeostasis of various cell types. Here we explored the role of chemokines, extracellular matrix production, and myofibroblast differentiation in self-assembled skin equivalents (SASE), a three-dimensional (3D) skin-equivalent tissue model. We found that the expression of three chemokines, C-C motif chemokine ligand (CCL) 20, C-X-C motif chemokine ligand (CXCL) 5, and CXCL8, increased with differentiation to myofibroblasts.

Self-Assembled Human Skin Equivalents Model Macrophage Activation of Cutaneous Fibrogenesis in Systemic Sclerosis.

Objective: The development of precision therapeutics for systemic sclerosis (SSc) has been hindered by the lack of models that accurately mimic the disease in vitro. This study was undertaken to design and test a self-assembled skin equivalent (saSE) system that recapitulates the cross-talk between macrophages and fibroblasts in cutaneous fibrosis.

Methods: SSc-derived dermal fibroblasts (SScDFs) and normal dermal fibroblasts (NDFs) were cultured with CD14+ monocytes from SSc patients or healthy controls to allow de novo stroma formation.

A Novel Three-Dimensional Skin Disease Model to Assess Macrophage Function in Diabetes.

A major challenge in the management of patients suffering from diabetes is the risk of developing nonhealing foot ulcers. Most methods to screen drugs for wound healing therapies rely on conventional 2D cell cultures that do not closely mimic the complexity of the diabetic wound environment. In addition, while three-dimensional (3D) skin tissue models of human skin exist, they have not previously been adapted to incorporate patient-derived macrophages to model inflammation from these wounds.

De novo production of human extracellular matrix supports increased throughput and cellular complexity in 3D skin equivalent model.

Three-dimensional (3D) tissue models of human skin are being developed to better understand disease phenotypes and to screen new drugs for potential therapies. Several factors will increase the value of these in vitro 3D skin tissues for these purposes. These include the need for human-derived extracellular matrix (ECM), higher throughput tissue formats, and greater cellular complexity.