How Far Are We from Research That Is Independent of the Use of Animal Models? A Comparative Analysis between Animal and 3D/On-a-Chip Models for the Study of Respiratory Diseases

Abstract

Over the last ten years, with the progress of in vitro culture methods, it has been possible to build increasingly reliable models to effectively mimic in vivo ones. The translational methodological approach that combined biotechnology and biomedical engineering has produced remarkable results, such as the development of ex vivo 3D culture models, the construction of on-a-chip organoids, and the construction of complex systems capable of bypassing the static nature of the two-dimensional cultural models that have been typical of in vitro studies conducted to date. However, nowadays, there is still reluctance to completely abandon the animal model as an essential reference or as an integrated step for the validation of a model or a proposed study. This is due to the partially correct conviction of the impossibility of reproducing, in vitro or ex vivo, the complexity of pathological models or the spatial communication between different cytotypes, as well as, more generally, the lack of systems capable of mimicking the dynamism of a complex in vivo system. In this study, we will compare different methodological approaches in the study of the three most common types of respiratory diseases: chronic obstructive pulmonary disease (COPD), asthma, and lung carcinomas. The purpose of this comparative study is to evaluate the most current methodological approaches to understand how far research is from being independent from animal models. Animal studies are generally considered necessary, but are still questioned because of the ethics and the cost–benefit ratio involved.