Non-animal models in dermatological research.

Elena Dellambra

doi:10.14573/altex.1808022

Abstract

Despite widely used for basic and preclinical studies in dermatology, available animal models only partly recapitulate human skin features often leading to disappointing outputs when preclinical results are translated to the clinic. Therefore, the need to develop alternative, non-animal models is widely recognized to more closely recapitulate human skin pathophysiology and to address the pressing ethical demand of reducing the number of animals used for research purposes, following the globally accepted 3Rs principle (Replacement, Reduction and Refinement). Skin is the outermost organ of the body, and, as such, easily accessible. Different skin cell types can be propagated in vitro and skin can be reconstructed for therapeutic transplantation as well as for in vitro modeling of physiopathological conditions. Bioengineered skin substitutes have been developed and evolved from elementary to complex systems, more and more closely resembling complete skin architecture and biological responses. In silico analyses take advantage from the huge amount of data already available from human studies for identifying and modeling molecular pathways involved in skin pathophysiology without further animal testing. The present review recapitulates the available non-animal models for dermatological research and sheds lights on their prospective technological evolution.

Highlights

The development of alternative models has gained a high priority following the European ban on animal testing for cosmetic ingredients (2009/1223/EU), the REACH guideline for chemicals (2006/1907/EC), and the recommendation to follow the 3R principle (Replacement, Reduction, Refinement) for research (2010/63/EU)
We investigated the expression of 90 ion channel genes in a total of 3673 patients reported in Oncomine, demonstrating that their expression was significantly modified in tumor samples and hypothesizing a relationship between such modifications and altered angiogenesis (Biasiotta et al, 2016)
Advanced glycation end products (AGEs) interact with AGE receptors and other receptors on fibroblasts that become activated and release either growth factors or cytokines involved in inflammatory responses or matrix metalloproteinases (MMPs) that remodel the dermal matrix (Okano et al, 2002; Molinari et al, 2008; Pageon, 2010)

Summary

Introduction

The development of alternative models has gained a high priority following the European ban on animal testing for cosmetic ingredients (2009/1223/EU), the REACH guideline for chemicals (2006/1907/EC), and the recommendation to follow the 3R principle (Replacement, Reduction, Refinement) for research (2010/63/EU). There is an extraordinary variety of non-animal models based on human cells and tissues representing a suitable alternative to replace animal studies for the cosmetic industry. Non-animal models represent a huge opportunity for pharmaceutical industry since an animal testing ban, while not mandatory at present, is foreseen in the future. Great efforts have been invested into developing models that more closely recapitulate in vivo skin complexity as tools for functional studies and to test therapeutic approaches. Improvements in non-animal models for dermatological research, especially skin equivalent techniques and in silico tools, will be discussed together with an overview of their application to the main fields of dermatological interest. A prospective view of further alternative method development will be given

Human skin structure

Animal models in dermatological research: potentials and limitations

Skin equivalents

In silico models

Immunological diseases

Conclusions