In vitro 3D co-culture model of human endothelial and smooth muscle cells to study pathological vascular remodeling

• Published in: Clínica e investigación en arteriosclerosis (Internet, English ed.) English ed.), 2024-11, Vol.36 (6), p.356-363
• Main Authors: San Sebastián-Jaraba, Irene, Fernández-Gómez, María José, Blázquez-Serra, Rafael, Sanz-Andrea, Sandra, Blanco-Colio, Luis Miguel, Méndez-Barbero, Nerea
• Format: Article
• Language: English
• Subjects: Cells communication; Comunicación celular; Célula de músculo liso vascular; Endotelio; Endothelial cells; Esferoides; In vitro; Remodelado vascular; Spheroids; Vascular remodelling; Vascular smooth muscle cells
• ISSN: 2529-9123; 2529-9123
• DOI: 10.1016/j.artere.2024.11.004

Pathological vascular remodeling of the vessel wall refers to the structural and functional changes of the vessel wall that occur in response to injury that eventually leads to cardiovascular disease (CVD). The vessel wall is composed of two main types of cells, endothelial cells (EC) and vascular smooth muscle cells (VSMC), whose communication is crucial in both the development of the vasculature and the homeostasis of mature vessels. Changes in the dialogue between ECs and VSMCs are associated with various pathological states that triggers remodeling of the vascular wall. For many years, considerable efforts have been made to develop effective diagnoses and treatments for these pathologies by studying their mechanisms in both in vitro and in vivo models. Compared to animal models, in vitro models can provide great opportunities to obtain data in a more homogeneous, economical and massive way, providing an overview of the signaling pathways responsible for these pathologies. The implementation of three-dimensional in vitro co-culture models for the study of other pathologies has been postulated as a potentially applicable methodology, which determines the importance of its application in studies of cardiovascular diseases. In this article we present a method for culturing human endothelial cells and vascular smooth muscle cells, grown under non-adherent conditions, that generate three-dimensional spheroidal structures with greater physiological equivalence to in vivo conditions. This in vitro modeling could be used as a study tool to identify cellular and molecular mechanisms involved in the pathological processes underlying vascular remodeling. El remodelado patológico de la pared vascular se refiere a los cambios estructurales y funcionales de la pared del vaso que ocurren en respuesta a una lesión que eventualmente conduce a una enfermedad cardiovascular (ECV). La pared de los vasos se compone de dos tipos principales de células, las células endoteliales (CEs) y las células del músculo liso vascular (CMLVs), cuya comunicación es crucial tanto en el desarrollo de la vasculatura como en la homeostasis de los vasos maduros. Cambios en el diálogo entre las CEs y las CMLVs se asocian a diversos estados patológicos que conllevan remodelado de la pared vascular. Durante muchos años se han realizado considerables esfuerzos dedicados al desarrollo de diagnósticos y tratamientos eficaces para estas patologías mediante el estudio de sus mecanismos tanto en modelo