Organoids The Work of the National Laboratory of Genetic Resources.

Organoids. The Work of the National Laboratory of Genetic Resources
 

Jesús Chimal-Monroy, Omar Collazo Navarrete, Gilda Guerrero Flores, Martha Elizabeth Montané Romero and Christopher Collazo Navarrete 

The brain is the center of cognitive abilities, of the individual’s interaction with the environment and of the maintenance of their vital functions. Like any other organ or tissue, the brain can suffer from injuries, infections, developmental disorders, and degenerative processes, which poses huge challenges for scientific research. The nervous system has been studied from various perspectives—from molecular and cellular to neural networks and brain structures—seeking to understand how they interact to generate functions such as thought, emotions, and body control. Both embryonic development and the disorders and diseases that affect its functioning are studied.

Research on the nervous system almost inevitably requires the use of animal models, mainly mammals, either through in vivo studies or through cell isolation and in vitro analysis.

The mouse (Mus musculus) stands out as an animal model because of its genetic similarity to humans, its short reproductive cycle, and because it is easy to manipulate genetically. The use of genetically modified mice has made it possible to understand biological processes related to health and disease that hadn’t been understood before. Despite significant advances in the use of animals, ethical debates have arisen about it.

This raises the challenge of reducing the use and costs associated with the maintenance of animals in research, for example, through the development of in vitro alternatives that reduce or replace in vivo studies.

In order to address ethical challenges, reduce the maintenance costs, and safeguard the transgenic mouse lines generated by the scientific community, the National Laboratory of Genomic Resources (LaNReGen) was established at UNAM’s Institute of Biomedical Research, with the mission of meeting the conservation needs of developed or acquired mouse strains by the scientific community in Mexico. In addition, we have the mission of contributing with alternatives to the use of animals accessible to the scientific community.

For this reason, at LaNReGen we have developed and implemented protocols for the cryopreservation of sperm and embryos in early stages of embryonic development. Cryopreservation allows us to store cells, tissues, organs, or organisms at -196° C, without losing their properties. In mouse embryos, this technique has been key to preserving animal models safely and efficiently, avoiding constant breeding and reducing costs and resources associated with their maintenance. We use the in vitro fertilization technique, which is very efficient for retrieving embryos in the two-cell stage. All cryopreservation procedures are performed in a controlled environment, ensuring efficient safeguarding, pathogen elimination, and safe re-entry of strains into pathogen-free conditions. So far, we have cryopreserved embryos of 30 strains, sperm of 91 strains and rederived 21 for pathogen cleaning from different institutions in the country.

On the other hand, we have developed in vitro models that allow us to study diseases and test drugs without resorting to live animals in early stages. Among these models are embryonic stem cell lines, useful for their ability to differentiate into any cell of the embryo. From these stem cells it is possible to generate organoids, which as their name indicates, are three-dimensional structures that resemble an organ in function and characteristics. During their in vitro formation, organoids recapitulate many of the processes that occur during embryonic development, a great advantage because they allow us to study everything from the formation to the functions of an organ and its structure, but under in vitro conditions. These characteristics make organoids very interesting experimental models in research for the generation of both basic and applied knowledge, reducing the use of animals.

At LaNReGen, we have successfully implemented this technology using the pancreas as a reference organ. We have established protocols, from human embryonic stem cells, to obtain organoids from exocrine cells, important in the study of pancreatic adenocarcinomas, and endocrine cells, relevant in the study of diabetes and other metabolic diseases. As for the pancreas, the infrastructure capabilities of LaNReGen, as well as the technical and intellectual capabilities of the laboratory staff, allow the implementation of the necessary protocols to generate different organoids that the scientific community may require, including those of the nervous system. See the work being done at LaNReGen in this video: https://youtu.be/2iP0KQM07XI?si=wWK9kACzpdcwCr7R.