Models for the study of nasal and sinus physiology in health and disease: A review of the literature

Abstract

ObjectiveChronic sinusitis is a very common yet poorly understood medical condition with significant morbidity. Hence, it remains an entity that is difficult to treat with unsatisfactory outcomes of current management options. This necessitates research into the etiology and pathophysiology of the condition to enhance our knowledge and the therapeutic options. Unfortunately, this kind of research is not always feasible on human subjects due to practical and ethical limitations. Therefore, an alternative model that simulates the disease had to be found in order to overcome these limitations. These models could either be in vivo or in vitro. The aim of our review is to summarize the research findings and key discoveries of both in vivo and in vitro models of chronic sinusitis that have enhanced our understanding of the condition today and have paved the way for the future research of tomorrow. Data Sources: PubMed literature review.MethodsA review of the literature was conducted to identify the main successful in vivo and in vitro models for chronic sinusitis.ResultsCreating a successful model for chronic sinusitis is no easy task. Over the years, both in vivo animal models and in vitro tissue culture models were proposed, with each model having its accolades and pitfalls, with the ideal model remaining elusive to this day. However, advancing three‐dimensional cell culturing techniques seems to be a promising new way to find a more accurate model.ConclusionNone of the current models is perfect for a thorough study of chronic sinusitis. However, three‐dimensional cell cultures have the potential to bridge the gap between in vivo and in vitro studies.Level of EvidenceNA

Comparative models for human nasal infections and immunity

“…1C) and therefore a full Waldeyer's ring similar to that of humans is not present (Casteleyn et al, 2011). Rabbits have been used as a model for paranasal sinuses fungal infections such as aspergillosis (Chakrabarti et al, 1997) as well as a model for rhinosinusitis (Al-sayed et al, 2017;Dao-yu et al, 2014). Strengths of the rabbit model include the anatomical similarities of the rabbit sinus with that of humans, the easy access to this area in rabbits and the fact that immune responses are largely conserved between rabbits and humans (Table 2).…”

Animal models for inflammatory mucosal disease and their potential for studying the microbiome in chronic rhinosinusitis

“…As an alternative to animal models, in vitro model systems provide some benefits for studying the aetiology and pathophysiology of diseases as they bypass major challenges such as variation among subjects and ethical issues associated with animal models (91) . A variety of cell culture methods has been employed to successfully recreate the human sinonasal epithelium (92) including the RPMI 2650 cell line, and monolayer cell cultures, which have been used in studies that obtained nasal tissue from humans (93,94) , as well as from rats, rabbits (95) , dogs, sheep and cattle (96) . Models derived from primary nasal epithelial cells of while the other nostril stays healthy mitigates the inter-subject variability that is a significant challenge in microbiome research.…”

“…Additionally, cultured nasal epithelial cells lose important characteristics over time such as ciliary function and the ability for mucin production, which represents major limitations especially for long-term studies (104) . A current review on models for sinonasal diseases highlights a more advanced 3D cell culturing method in which the cells of the basal side reside within the culture medium while the apical surfaces of cells are surrounded by air (92) . The so called air-liquid-interface (ALI) culture mimics the natural environment of nasal epithelial cells and has become the method of choice for such studies (105,106) .…”

“…The so called air-liquid-interface (ALI) culture mimics the natural environment of nasal epithelial cells and has become the method of choice for such studies (105,106) . ALI cultures are still not ideal as models of CRS due to the applied culturing techniques interfering with natural cellular behaviour (92) . Recently, more complex culturing systems have been developed to overcome these problems.…”

“…In vitro models circumvent the translational discrepancy between animal models and humans, hence 3D cell culturing can be considered a powerful tool for future studies on inflammatory nasal disease in humans (92) . As this review focuses on model systems especially suitable for research on the nasal microbiome in CRS, it has to be mentioned that presently in vivo models are markedly superior to in vitro cell culture models because the latter cannot mimic the dynamics between inflammation, immune response and the host microbiome (92) . Future that make it particularly suitable for microbiological research in a pre-clinical setting (87) .…”