Experimentación preclínica en modelos humanos

Abstract

The rough endoplasmic reticulum (ER) is an organelle which contributes to cell homeostasis. When that cellular equilibrium is broken, ER acts as a stress sensor and activates the misfolded protein pathway (UPR), key to control cell fate decisions. Seipin is a transmembrane protein of the RER encoded by BSCL2 gene and its localization is ubiquitous. It is a multifunctional molecule, whose possible functions in the organism are still being hypothesized. However, it is known that it plays a fundamental role in lipid metabolism. At the cellular level, seipin is essential in the adipocyte differentiation and, at the tissue level, it is considered a tissue-dependent protein highly relevant in the gonads, liver and nervous tissue. Therefore, the synthesis of an aberrant, mutated seipin and/or its aggregation will lead to pathologies mainly related to previously mentioned tissues and all of them are called seipinopathies. Due to the fact that the disorders included in this group are immeasurable, this Final Degree Project will focus into reviewing lipodystrophy type 2 and neurodegenerative diseases; the latter mentioned, from a more generalized point of view, due to their lack of knowledge because of their recent appearance in the literature.

In recent years there has been a need to use and develop new human models of preclinical experimentation that more accurately reflect the biological characteristics of human beings. Currently, three-dimensional human models have been developed that, together with the incorporation of biomedical engineering techniques and artificial intelligence, have represented an important advance in the field of preclinical research. This literature review will aim to present an updated summary of certain human models of interest available for preclinical research. The evolution from 2D cell cultures to human three-dimensional (3D) models will be analyzed to address the most promising preclinical models such as spheroids, organoids and assoids derived from human cells. In addition, the main characteristics, limitations and applications of the same will be exposed. Finally, examples of intestinal and brain organoids will be described in more detail, as well as some diseases that have benefited from the study with organoids in recent years