Three-Dimensional Cell Cultures as a Research Platform in Lung Diseases and COVID-19

Abstract

Background: Chronic respiratory diseases (CRD) are a major public health problem worldwide. In the current epidemiological context, CRD have received much interest when considering their correlation with greater susceptibility to SARS-Cov-2 and severe disease (COVID-19). Increasingly more studies have investigated pathophysiological interactions between CRD and COVID-19. Area covered: Animal experimentation has decisively contributed to advancing our knowledge of CRD. Considering the increase in ethical restrictions in animal experimentation, researchers must focus on new experimental alternatives. Two-dimensional (2D) cell cultures have complemented animal models and significantly contributed to advancing research in the life sciences. However, 2D cell cultures have several limitations in studies of cellular interactions. Three-dimensional (3D) cell cultures represent a new and robust platform for studying complex biological processes and are a promising alternative in regenerative and translational medicine. Expert opinion: Three-dimensional cell cultures are obtained by combining several types of cells in integrated and self-organized systems in a 3D structure. These 3D cell culture systems represent an efficient methodological approach in studies of pathophysiology and lung therapy. More recently, complex 3D culture systems, such as lung-on-a-chip, seek to mimic the physiology of a lung in vivo through a microsystem that simulates alveolar-capillary interactions and exposure to air. The present review introduces and discusses 3D lung cultures as robust platforms for studies of the pathophysiology of CRD and COVID-19 and the mechanisms that underlie interactions between CRD and COVID-19.

Better In Vitro Tools for Exploring Chlamydia trachomatis Pathogenesis

“…Three-dimensional (3D) cell-culture models based on primary cells are acquiring great importance as a new and robust platform for studying complex biological processes and might be a promising alternative in C. trachomatis pathogenetic studies [ 13 ]. In this regard, 3D models might help in recreating the microenvironment that C. trachomatis encounters in the host tissue, allowing a deeper understanding of host–pathogen interactions since these systems promote direct cell-to-cell contact, interactions of cells with the extracellular matrix and in vivo like exchange of soluble factors [ 10 , 11 ]. Furthermore, 3D cell culture models are known to retain the cellular structure and spatial orientation more closely resembling the in vivo parental tissue than the more widespread 2D cell culture models [ 10 , 11 ].…”

“…In the literature, several approaches have been developed for generating 3D models (Table 1), including scaffold-based 3D cultures, that use matrices for cells adhesion, and non-scaffold 3D cultures, that, by contrast, lead to cell assembly into spheroids. The nonscaffold 3D cultures promote cell-to-cell rather than cell-to-extra cellular matrix interactions, favoring the natural aggregation and assembly of cells in spheroids that better mimic the in vivo organ formations, hence the name organoids [10,11,46]. Amongst the different methodologies, 3D bioprinting technologies have opened a completely new field for tissue engineering [47].…”

“…Specifically, several in vitro cellular models, based on two-dimensional (2D) cultures of immortalized cells, have been employed for investigating C. trachomatis host–cell interaction, focusing on the characteristics of chlamydial developmental cycle and its intracellular survival strategies. These systems have been very useful due to their highly controlled experimental conditions, although they fail to mimic the complex and dynamically changing structure of in vivo human host-tissues [ 10 , 11 ]. As a way to overcome these issues, in vivo animal models, mainly mice, have been used to elucidate the natural history of the disease, the pathogenetic mechanisms underlying chlamydial infection and its chronic outcomes, as well as for drug and vaccine development; however, animal models possess important differences from the human host in the clearance of chlamydial infection and in the defense immune mechanisms [ 12 , 13 ].…”

Mesenchymal Stem Cell-Derived Extracellular Vesicles in the Management of COVID19-Associated Lung Injury: A Review on Publications, Clinical Trials and Patent Landscape

“…Subsequent to completion of these studies, a comprehensive meta-analysis could derive an effective MSC-EVs based therapeutic regime for the management of acute lung injury in the context of COVID19. Several notable works have been reported recently on various aspects of stem cells and exosomes in the context of COVID19 [ 20 – 23 ]. However, this review standout as a unique collection of the current landscape in terms of preclinical, clinical and patent data sets reported to date.…”

Ultracellular Imaging of Bronchoalveolar Lavage from Young COVID-19 Patients with Comorbidities Showed Greater SARS-COV-2 Infection but Lesser Ultrastructural Damage Than the Older Patients

“…Though it has been described that the SARS-CoV-2 establishes an interaction with host cells through the angiotensin-converting enzyme 2 (ACE2) receptors (Zhang et al, 2021), other reports suggest that the virus can infect any epithelial cells of the oropharyngeal mucosa and respiratory tract, including endothelial cells, especially in severe disease and ARDS condition after cytokine storm irrespective of the presence of ACE2 receptors (Zamorano Cuervo & Grandvaux, 2020; Liu et al, 2021). Organoid culture (2D and 3D) studies on human bronchial and lung epithelial cells revealed no SARS-CoV-2 cellular tropism or ultrastructural alteration (Elbadawi & Efferth, 2020; Salahudeen et al, 2020; da Silva da Costa et al, 2021). Transmission (for cellular ultrastructure) and scanning (for surface ultrastructure) electron microscopic and immunofluorescence (for analysis of cellular infection) studies can directly explore the SARS-CoV-2 infection in different cells of bronchoalveolar fluid (BALF), that provide direct evidence of cellular infection load and ultrastructural changes in old and young patients with comorbidities such as diabetes, liver and kidney diseases, and malignancies.…”