Abstract
The use of human organotypic models for biomedical research is experiencing a significant increase due to their biological relevance, the possibility to perform high-throughput analyses, and their cost efficiency. In the field of anti-infective research, comprising the search for novel antipathogenic treatments including vaccines, efforts have been made to reduce the use of animal models. That is due to two main reasons: unreliability of data obtained with animal models and the increasing willingness to reduce the use of animals in research for ethical reasons. Human three-dimensional (3-D) models may substitute and/or complement in vivo studies, to increase the translational value of preclinical data. Here, we provide an overview of recent studies utilizing human organotypic models, resembling features of the cervix, intestine, lungs, brain, and skin in the context of anti-infective research. Furthermore, we focus on the future applications of human skin models and present methodological protocols to culture human skin equivalents and human skin explants.
Highlights
Overall mortality caused by infectious diseases has dramatically decreased in the past decades due to the positive impact of antibiotics, antivirals, antifungals, vaccines, and more recently monoclonal antibodies
We will dedicate a section of this review to human skin models commenting on their future applications and presenting a methodological protocol for the culture of human skin explants and skin equivalents that can be applied to anti-infective research
A study performed in a human full-thickness skin equivalent, constructed by keratinocytes and fibroblasts seeded on top of a de-epidermalized dermis (DED) scaffold, showed that a tetraspanin-derived peptide can halve the number of S. aureus adherent to keratinocytes as compared to a scrambled control peptide, without impairing keratinocyte viability (Ventress et al 2016)
Summary
Overall mortality caused by infectious diseases has dramatically decreased in the past decades due to the positive impact of antibiotics, antivirals, antifungals, vaccines, and more recently monoclonal antibodies. The use of in vitro and/or in vivo models in preclinical research aims to predict the level of safety, immunogenicity, and protection of novel anti-infective treatments. There is an abundant amount of pathogens with exclusive human-specific properties, underlining the need for human in vitro or ex vivo models to study these microbes and to obtain reliable results in preclinical studies. We will present an overview of human organ-specific models used in anti-infective research, focusing on cervical, intestinal, respiratory, brain, and skin models. We will dedicate a section of this review to human skin models commenting on their future applications and presenting a methodological protocol for the culture of human skin explants and skin equivalents that can be applied to anti-infective research
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