Human Organotypic Models for Anti-infective Research

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.

Repurposing of the antibiotic nitroxoline for the treatment of mpox

“…To investigate the antiviral effects of nitroxoline in the context of the skin architecture, we used primary human split-thickness skin grafts that preserve the histology and complexity of the skin [Hendriks et al, 2021]. Skin grafts were infected with 10 6 TCID50/mL of mpox virus isolate 1 (MPXV1), and the infection was visualised by immunohistochemical staining for virus antigen after 48h.…”

Repurposing of the antibiotic nitroxoline for the treatment of mpox

“…To investigate the antiviral effects of nitroxoline in the context of the skin architecture, we used primary human split-thickness skin grafts that preserve the histology and complexity of the skin. 37 Skin grafts were infected with 10 6 TCID50/mL of mpox virus isolate 1 (MPXV1), and the infection was visualised by immunohistochemical staining for virus antigen after 48 h. As depicted in Figure 1H, pronounced infection was detected in the epidermis. Moreover, clusters of infected cells or single infected cells were located in the dermis (Figure 1H).…”

Biomaterial strategies to replicate gynecological tissue

“…125 Organotypic models can be used as a platform to evaluate cell adhesion and invasion. 126,127 A 3D co-culture model based on omentum with three layers of cell types and ECM (fibronectin and collagen type I) was used to analyze the effect of drug combinations on cell adhesion and proliferation. 128,129 After ovarian cancer cells attach and clear through the mesothelial cell lining, they spread along the underlying ECM, remodel the ECM, and proliferate.…”