Three-Dimensional Rotating Wall Vessel-Derived Cell Culture Models for Studying Virus-Host Interactions

Abstract

The key to better understanding complex virus-host interactions is the utilization of robust three-dimensional (3D) human cell cultures that effectively recapitulate native tissue architecture and model the microenvironment. A lack of physiologically-relevant animal models for many viruses has limited the elucidation of factors that influence viral pathogenesis and of complex host immune mechanisms. Conventional monolayer cell cultures may support viral infection, but are unable to form the tissue structures and complex microenvironments that mimic host physiology and, therefore, limiting their translational utility. The rotating wall vessel (RWV) bioreactor was designed by the National Aeronautics and Space Administration (NASA) to model microgravity and was later found to more accurately reproduce features of human tissue in vivo. Cells grown in RWV bioreactors develop in a low fluid-shear environment, which enables cells to form complex 3D tissue-like aggregates. A wide variety of human tissues (from neuronal to vaginal tissue) have been grown in RWV bioreactors and have been shown to support productive viral infection and physiological meaningful host responses. The in vivo-like characteristics and cellular features of the human 3D RWV-derived aggregates make them ideal model systems to effectively recapitulate pathophysiology and host responses necessary to conduct rigorous basic science, preclinical and translational studies.

IL-36γ induces a transient HSV-2 resistant environment that protects against genital disease and pathogenesis

“…As a potential host defense mechanism in response to HSV-2 infection, we sought to determine the level to which IL-36γ impacted HSV-2 replication in a well-characterized 3-D human VEC model [33]. Three-dimensional VEC aggregates were treated with IL-36γ (100 ng/ml or 500 ng/ml) or poly(I:C) (100 μg/ml) 24h prior or 4h prior to HSV-2 challenge.…”

Role of Tissue Engineering in COVID-19 and Future Viral Outbreaks

“…These models simulate low physiologic shear stresses and frequently incorporate multiple pulmonary cell types, including coculture of human mesenchymal bronchial tracheal cells and human bronchial epithelial cells, challenging them against respiratory syncytial virus and SARS-CoV-1. 33 Unfortunately, SARS-CoV-1 did not replicate in this study. 34 In another model, human pulmonary epithelial progenitor cells were grown on a collagen matrix in a serum-free media with a mesenchymal stroma and exposed to virus.…”

Nanoparticle-mediated drug delivery to treat infections in the female reproductive tract: evaluation of experimental systems and the potential for mathematical modeling

“…Although a comprehensive review of available cell culture models may be found in the studies by He et al, 74 hallmark studies relevant to FRT delivery are included in several studies. 44,69,73,74,76,77,84,85 ex vivo transport studies…”

“…To more faithfully represent the mucosal environment, more advanced in vitro systems such as synthetic mucus, 69 undiluted CVM collected from human patients, 11,20,30,31,35,[70][71][72] and 3D cell culture techniques have been developed. 27,28,52,55,[73][74][75][76][77] In addition to utilizing a relevant model to study and obtain transport information, essential physical and chemical properties must be considered to effectively design NPs to navigate the CVM. Depending on whether mucoadhesive or muco-inert properties are preferred, these properties may be tailored to enhance distribution through mucus and to the underlying epithelial and stromal cell layers.…”