Mini laboratory lungs to study respiratory diseases

Research advances in every way, to the point that they can already be reproduced in a laboratory mini primary human organs to model any disease. This is the case carried out by a team from the ISCIII, where they have launched a new model to study pneumococcus. This strategy stands out for having developed pulmonary organoids or what is the same, mini lungs generated with embryonic pluripotent stem cells, whose objective is mimic the activity of a real lung.

Alberto Zambranomain author of the study and researcher at the ISCIII in the Functional Unit for Research in Chronic Diseases, explains to Gaceta Médica that, once these mini-lungs are generated, they introduce the bacteria and attempts to reproduce the transit or infection that takes place in the respiratory system.

“These mini lungs are generated through embryonic cells where all the information, all the structure and part of the function of the original lung is collected, in such a way that it serves as a model of native, original and abrupt organs”

Alberto Zambranolead author of the study.

As he explains, they have been able to follow the bacteria, to study the innate response of the host and to reproduce all the important events of a pneumococcal disease, in such a way that this will now serve to test antibiotics or antimicrobial agentas well as the virulence factors that bacteria can use.

A revolution, now that it is becoming more and more difficult to work with rodents as many ethical criteria are required. This model is already seen as an advantage over more traditional ones, the researcher points out. However, Zambrano believes that he still cannot be replaced and is in favor of keeping animal models in laboratories since “a live context gives them additional information as well, the organoids are complementary at the moment”.

The investigator of ISC III shows that this new model of mini lungs is a totally sophisticated system by representing a real lung in a few millimeters. And it is that it does not lack detail since it collects all the cells, from the ducts to the trachea, bronchi, bronchioles and alveoli to represent any respiratory, infectious or rare disease and, in this way, researchers can better understand their behavior when it occurs in humans.

“These little lungs well reproduce the structure and function of the original organ and they serve to model any human respiratory disease, which facilitates the search for new targets with therapeutic interest and the testing of new compounds”, emphasizes the researcher.

These organoids have several applications from disease modelingas is the case of the study where they wanted to analyze the pneumococcus, a bacterium that causes diseases such as pneumonia or meningitis, until the evaluation of any compound of interest against any disease or antibiotics.

Likewise, Zambrano points out that we cannot forget the gene therapy and alternative medicine since in the future it will be possible to generate patient tissue to use as a transplant. “These mini-organs will lay the foundations for future regenerative medicine,” warns the researcher.

Endless uses with a clear objective: model the disease to understand it better and seek the appropriate therapy through multiple antimicrobial agents, antiviral agents, compounds against rare diseases or oncological diseases. Zambrano says that being a primary and normal model, any disease can be modelled. “For example, I can mutate it and generate a small tumor or use mutagenic agents such as tobacco smoke in liquid form and see how it is altering the genetics of the lung epithelium itself,” he explains.

The beginnings

East “ideal model” of organoids is something recentIt hasn’t been in the labs for even ten years. Alberto Zambrana says that the first article on the differentiation of pluripotent cells into mini lungs appeared in 2014 and the protocol in 2015.

From that moment, Zambrano, as a good researcher, became interested and requested permission to start working on this type of model. First, in 2017, with a dimensional structure and later in three dimensions, “which was a great advance since it reproduced the structure and its function”. And to date, numerous investigations have been carried out on these organoids that, it seems, will serve a great deal.

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