One of the greatest challenges in science in our century is to seek alternatives to animal experimentation. Unfortunately, on many occasions it is still unavoidable to use animal models to understand the mechanisms that trigger a disease or to test new drugs, although it is true that the number of animals used in trials is decreasing every year.
For this, the maximum of the 3Rs (Reduction, Refinement and Replacement) prevails: reduce the number of animals used, refine the experimental conditions to guarantee their maximum welfare and, whenever possible, try to replace the animal models with other experimental methods.
Many research groups are already working on the alternatives, and one example is the laboratory of Professor Alfonso Martínez Arias, in the Department of Genetics at the University of Cambridge. His team has been studying the mechanisms that lead a group of cells to form differentiated embryos for years and recently discovered that, under certain conditions, stem cells from laboratory mice can organize themselves into three-dimensional aggregates that show characteristics of the first stages. of embryonic development. They are baptized as ‘gastruloids’, and could be an alternative to the use of authentic embryos, with all the ethical problems that this option entails.
An alternative to using mammalian embryos
In an article recently published in the journal Nature , and the result of an international collaboration with other universities, the team shows how in gastruloids the formation of the three main embryonic axes follows a gene expression program very similar to that of authentic embryos. Therefore, these structures created artificially from stem cells have great potential to serve as a model that allows studying the initial stages of embryonic development in mammals , both that which occurs normally and that which presents some pathology. .
“To determine whether gastruloids are organized into authentic embryonic structures, we characterize their level of genetic activation at different stages of development,” explains Denis Duboule, a researcher at the University of Geneva. The scientists identified and quantified transcribed RNA from gastruloids and compared the expressed genes with those from mouse embryos at comparable stages of development.
“The gastruloids form structures similar to the posterior part of the embryo, whose developmental program is somewhat different from that of the head”, explains Leonardo Beccari, co-author of the study. These pseudo-embryos express characteristic genes of the various types of progenitor cells necessary for the constitution of future tissues. “The complexity of gene expression profiles increases over time, with the appearance of markers from different embryonic cell lineages, just like in the profiles observed in control embryos”, says Naomi Moris, a scientist from the Cambridge team .
Hox genes are activated
Another surprising and hopeful finding was related to the Hox genes, a set of genes highly involved in embryonic development and which would be a kind of ‘architects’ of this complex process. In gastruloids grown in vitro, the Hox genes were activated in the same sequential order as in normal embryos. “The implementation of the Hox gene network over time, which mimics that of the embryo’s tail, confirms the surprisingly high level of self-organization of gastruloids,” said Mehmet Girgin, another geneticist who co-authored the work.
In Hox we trust
#InHoxWeTrust . This is the hashtag chosen by the tweeting researchers who have participated in this research to celebrate the publication of their article in Nature . Alfonso Martínez Arias and Denis Duboule are two of the most active authors in this social network and whose profiles are worth following to learn more about gastroluides and the ins and outs of their research.
Referencia: Beccari et al. 2018. Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids. Nature https://doi.org/10.1038/s41586-018-0578-0DO.
Foto: © Mehmet Girgin, EPFL
