Fibroblasts and Endothelial Cells in Three-Dimensional Models: A New Tool for Addressing the Pathogenesis of Systemic Sclerosis as a Prototype of Fibrotic Vasculopathies

Description

Abstract

Abstract: Two-dimensional in vitro cultures have represented a milestone in biomedical and phar-
macological research. However, they cannot replicate the architecture and interactions of in vivo
tissues. Moreover, ethical issues regarding the use of animals have triggered strategies alternative to
animal models. The development of three-dimensional (3D) models offers a relevant tool to investi-
gate disease pathogenesis and treatment, modeling in vitro the in vivo environment. We aimed to
develop a dynamic 3D in vitro model for culturing human endothelial cells (ECs) and skin fibroblasts,
simulating the structure of the tissues mainly affected in systemic sclerosis (SSc), a prototypical
autoimmune fibrotic vasculopathy. Dermal fibroblasts and umbilical vein ECs grown in scaffold or
hydrogel, respectively, were housed in bioreactors under flow. Fibroblasts formed a tissue-like texture
with the deposition of a new extracellular matrix (ECM) and ECs assembled tube-shaped structures with
cell polarization. The fine-tuned dynamic modular system allowing 3D fibroblast/EC culture connection
represents a valuable model of the in vivo interplay between the main players in fibrotic vasculopathy
as SSc. This model can lead to a more accurate study of the disease’s pathogenesis, avoiding the use of
animals, and to the development of novel therapies, possibly resulting in improved patient management