Organoids show potential in detecting specific mutations and the effect of drugs in various pathologies

Marimar Encabo Berzosa, technician at the Biobank of the Aragon Health System (BSSA), explains to Gaceta Médica at what point its development and application is.

In the research and study of different diseases, the use of animals is common. However, the latest advances in stem cell technology and bioengineering have made it possible to develop organoids, also commonly known as 'miniature organs', that simulate the properties of organs or tissues and are destined to be a 'revolution'. In this sense, Marimar Encabo Berzosa, doctor in nanotechnology and technician from the Biobank of the Aragon Health System (BSSA), explains to Gaceta Médica the main characteristics and functionalities of organoids, in addition to the point at which their development is.

Until a few years ago, diseases and drugs were studied using a monolayer of cells grown in the laboratory. Therefore, organoids are designed to be as similar as possible to the natural state of the cells within an organ.: constituted in three dimensions and interacting with other cell types.

“We can define an organoid as a three-dimensional in vitro model which originates from different cell types. It always comes from stem cells, which can be pluripotent or adult stem cells,” explains Encabo. Furthermore, the expert adds that “in the case of the Biobank of Aragon, adult stem cells derived from any type of tissue are always used. This allows the organoids to have the ability to self-regenerate and differentiate in a similar way to how the fabric from which it is created does.”

Disease models

Being able to develop structures that maintain the identity of the tissue or the organ from which they are derived allows the organoids to present multiple applications. From providing data to develop drugs to evaluating which medication is best for each patient, this is linked to personalized medicine. “Organoids are not only useful for cancer, but also for studying other diseases, such as cystic fibrosis. In this case, we could take the damaged tissue, generate an organoid that simulates that disease and test drugs or see specific mutations of the disease,” says the BSSA expert.

The development of these structures is carried out based on tumor tissue, healthy tissue or any pathology. “The stem cells that come from these tissues are isolated, first by performing a mechanical disintegration and then performing an enzymatic treatment that will isolate those cells from the tissue matrix,” explains Encabo. "Then we put these cells in culture with specific factors that keep them inside a matrix that will try to simulate the extracellular matrix that we have in our tissues and that is made up of collagen and laminin,” he adds. As a result, and after several days in an incubator, three-dimensional structures are formed, like accumulations of cells, which simulate the tissue from which it is started.

When creating different organoids, it must be taken into account that, depending on the type, each one will have its particularities. Currently, the most developed are the organoids derived from epithelial cells. However, at the BSSA “work is being done on the development of glioblastoma organoids. What we do is take a piece of the brain tumor, chop it up and culture it in suspension. The cells are added to each other and we do not use matrices,” the specialist emphasizes.

Latest advances

In the case of epithelial tissue, organoids of all types of tissues have been developed, but advances are beyond the human species. “The most powerful group today is that of the geneticist Hans Clevers, who is in the Hubrecht Institute of Holland, and that has developed snake venom gland organoids,” says Encabo.

Clevers' group studies the molecular mechanisms of tissue development and cancer of various organs using engineered organoids from Lgr5 adult stem cells. The latest work they have published in the journal Cancer Cell analyzes the dependencies of pharmacological growth and tumor evolution in organoids derived from patients with neuroendocrine neoplasias.

“A new type of culture called 'asembloid' has emerged, which joins different types of organoids to simulate something more similar to what the complete organism is”

Marimar Encabo, technician at the Biobank of the Aragon Health System (BSSA)

“Some organoids, such as brain organoids, are more complicated to create due to the complexity of the nervous system, but the advances we are experiencing in this field are very powerful,” the expert emphasizes. In this sense, Encabo points out that “a new type of crop called 'asembloid', which what it does is join together different types of organoids to simulate something more similar to what the complete organism is.”

In addition to brain organoids, Another type of tissue that is difficult to develop is cartilage and bone.. “Organoids also have limitations because, for example, they do not have a vascular system as such or an immune system. What is being done now is trying to combine everything, that is, generating organoids that also have a vascular system and joining it with the tissue organoid in culture,” adds the BSSA expert.

However, there are other ways to put it all together. “You can put the organoids in a kind of fluid culture flash that simulates that vascular system or you can also make a organoid coculture with the immune system depending on what you want to study,” explains Encabo. “It is a technique that is increasingly advanced, but there is still a long way to go because we do not have all the cell types of the tissue represented. In addition, it is also necessary to make the model more complex, going from an organoid to the most complete organism,” he highlights.

Future of organoids

One of the focuses on which medical research is focused is personalized medicine and the use of organoids as well. “Organoids are beginning to be applied in personalized medicine. For example, in the case of cancer, a sample of the biopsy of each patient's tumor would have to be taken and a specific organoid generated from it,” says Encabo. In this case, different chemotherapy agents could be tested and check “quite accurately,” as the expert points out, how they would influence the patient and which would be most effective in eliminating the tumor.

At the Biobank of Aragon they have been able to develop different types of organoids, both healthy and tumor tissue from the kidney, colon, breast and central nervous system. But, in addition to this, they are currently not only working on its development, but also on the characterization of these tissues.

Source: Medical Gazette