Organoids are poised to revolutionize the study of disease, drugs and personalized medicine.

The use of animals is common in the research and study of various diseases. However, recent advances in stem cell technology and bioengineering have enabled the development of organoids, also commonly known as “miniature organs,” which mimic the properties of organs or tissues and are set to bring about a “revolution.” In this sense, Marimar Encabo Berzosa, Doctor of Nanotechnology and Technician at the Biobank of the Aragon Health System (BSSA)explains Gaceta Médica the main characteristics and functionality of organoids, as well as the point of their development.

Until a few years ago, diseases and drugs were studied using a monolayer of cells grown in the laboratory. Therefore, organoids are designed to closely match the natural state of the cells within the organ.: Consists of three dimensions and interacts with other cell types..

“We can define an organelle as 3D in vitro model which comes from different types of cells. It always comes from stem cells, which can be pluripotent or adult stem cells,” Encabo explains. In addition, the expert adds that “in the case of the Biobank of Aragon, adult stem cells obtained from any type of tissue are always used. This allows organelles to have ability for self-healing and differentiation similar to the action of the fabric from which it is made.”

Disease models

The ability to create structures that retain the identity of the tissue or organ from which they originated allows organoids to represent several applications. From providing data for drug development to assessing which drug is best for each patient, it’s all about personalized medicine. “Organoids are useful not only in cancer, but also in the study of other diseases, such as cystic fibrosis. In this case, we could take the damaged tissue, create an organoid that mimics the disease, and test drugs or see specific mutations of the disease,” says the BSSA expert.

The development of these structures is carried out on the basis of tumor tissue, healthy tissue or some pathology. “Stem cells coming from these tissues are isolated, first by mechanical disintegration followed by enzymatic treatment this isolates these cells from the tissue matrix,” explains Enkabo. “Then we put these cells in culture with certain factors that keep them inside a matrix that will try to mimic the extracellular matrix which is found in our tissues and consists of collagen and laminin,” he adds. As a result, after a few days in the incubator, three-dimensional structures like clusters of cells are formed, imitating the tissue from which it originated.

When creating various organelles, it is necessary to take into account that, depending on the type, each of them will have its own characteristics. Currently the most developed are organoids derived from epithelial cells. However, at GABSA, “work is underway to develop glioblastoma organoids. What we do is take a piece of the brain tumor, grind it up and culture it in suspension. The cells stack on top of each other, and we do not use matrices,” the specialist emphasizes.

Latest Developments

In the case of epithelial tissue, organoids of all tissue types have been developed, but advances have not yet been made. beyond the human race. “The most influential group today is that of geneticist Hans Clevers, who works at the Hubrecht Institute in Holland and developed snake venom gland organoids,” says Enkabo.

Clevers’ group studies the molecular mechanisms of tissue development and cancer in various organs using engineered organoids. from Lgr5 adult stem cells. The latest work, published in the journal Cancer Cell, analyzes the relationship between pharmacological growth and tumor evolution in organoids obtained from patients with neuroendocrine neoplasias.

“A new type of culture has emerged called an asembloid, which combines different types of organelles to mimic something more akin to what a complete organism would be like.”

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

“Some organoids, such as brain organoids, are more difficult to create due to the complexity of the nervous system, but the advances we are seeing in this area are very powerful,” the expert emphasizes. In this sense, Enkabo points out that “a a new type of crop called “asembloid”.which combines different types of organelles to mimic something more like a complete organism.”

Current restrictions

In addition to brain organelles, Another type of tissue that is difficult to develop is cartilage and bone.. “Organoids also have limitations because, for example, they don’t have a vascular system per se or an immune system. Now an attempt is being made to combine everything, that is, to create organoids that also have a vascular system, and connect them with a tissue organoid in culture,” adds the BSSA expert.

However, there are other ways to put it all together. “You can put organelles in a kind of flash liquid culture which simulates this vascular system, or you can also do organoid coculture with the immune system, depending on what you want to study,” Encabo explains. “This is a technique that is becoming more advanced, but it still has a long way to go because we don’t have all the cell types in the tissues represented. In addition, it is also necessary to complicate the model, moving from an organoid to the most complete organism,” he emphasizes.

The future of organoids

One of the areas of medical research is personalized medicine and the use of organoids: “Organoids are beginning to be used in personalized medicine. For example, in the case of cancer, it would be necessary to take a biopsy sample from each patient’s tumor and obtain a specific organoid from it,” says Encabo. In this case, it would be possible to test different chemotherapy drugs and “quite accurately,” as the expert points out, check how they would affect the patient and which ones would be most effective in eliminating the tumor.

At the Aragon Biobank they were able to develop different types of organoids, both healthy and tumor tissues from the kidneys, colon, breast and central nervous system. But, besides this, they are currently working not only on its development, but also on creating characteristics of these fabrics.

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