In the research and study of various 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’, which mimic the properties of organs or tissues and are set to be ‘revolutionary’. In this sense, Marimar Encabo Berzosa, Doctor of Nanotechnology and Technician of the Biobank of the Aragon Health System (BSSA)Gaceta Médica explains the main characteristics and functions of organoids, as well as the point of their development.
Until a few years ago, diseases and drugs were studied using monolayers of cells grown in the laboratory. Therefore, organoids are designed to mimic the natural state of cells within an organ as closely as possible.: Structured in three dimensions and interacts with other cell types.
“We can define an organoid as a A three-dimensional in vitro model which are produced from different types of cells. It always comes from stem cells, which can be pluripotent or mature stem cells,” Encabo explains. Moreover, 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 the organoids Ability to self-regenerate and differentiate So does the fabric from which it is made.”
Being able to develop structures that retain the identity of the tissue or organ from which they are derived allows organoids to present. Multiple applications. This is linked to personalized medicine, providing data to develop medicines to assess which medicine is best for each patient. “Organoids are useful not only for cancer, but also for studying other diseases like cystic fibrosis. In this case, we can take damaged tissue, generate an organoid that mimics that disease and test drugs or One can see the specific mutations of the disease,” says the BSSA expert.
Development of these structures is carried out on the basis of tumor tissue, healthy tissue or any pathology. “Stem cells from these tissues are isolated, first a Mechanical disintegration followed by enzymatic treatment It will separate those cells from the tissue matrix,” Encabo explains. “Then we put these cells in culture with specific factors that keep them within a matrix that will attempt to mimic the extracellular matrix which is in our tissues and is made up of collagen and laminin,” he adds. As a result, and after several days in the incubator, three-dimensional structures are formed, such as clusters of cells, that mimic the tissue from which they start.
When creating different organoids, it must be taken into account that, depending on the type, each will have its peculiarities. Currently, the most developed Organelles derived from epithelial cells. However, development of “glioblastoma organoids” is being worked on at BSSA. What we do is take a piece of brain tumor, cut it out and culture it in suspension. The cells are added to each other and we do not use matrices,” emphasizes the expert.
In the case of epithelial tissues, all types of tissue organoids have been developed, but are advanced. outside the human race
. “The most powerful group today is that of geneticist Hans Clavers, who is at the Hubrecht Institute in Holland and has developed snake venom gland organoids,” says Encabo.Clavers’ group studies the molecular mechanisms of tissue development and cancer in various organs using engineered organoids. Lgr5 from adult stem cells. Their latest work, published in the journal Cancer Cell, analyzes the dependence of pharmacological growth and tumor evolution in organoids obtained from patients with neuroendocrine neoplasms.
“A new type of culture called the ‘assembloid’ has emerged, combining different types of organoids to form something more like a complete organism”
Marimar Encabo, technician at the Biobank of the Aragon Health System (BSSA).
“Some organoids, such as brain organoids, are more complicated to make because of the complexity of the nervous system, but the progress we are experiencing in this area is very powerful,” emphasizes the expert. In this sense, Encabo points out that “A A new crop called ‘Assembloid’What it does is bind together different types of organoids to make something more like a complete organism.”
In addition to brain organelles, Other types of tissue that are difficult to develop are cartilage and bone.. “Organoids also have limitations because, for example, they don’t have a vascular system or an immune system. What’s being done now is trying to combine everything, that is, producing organoids that have a vascular system and growing them in tissue in culture. Connecting with the organoid,” adds the BSSA expert.
However, there are other ways to put it all together. “You can put organoids into a type Liquid culture flash Which simulates that vascular system or you can make one too Organoid Coculture with the immune system depending on what you want to study,” Encabo explains. “It’s a technique that’s getting more and more advanced, but there’s still a long way to go because we don’t have all the cell types of the tissue. Furthermore, it is also necessary to further complicate the model moving from the organoid to the most complete organism,” he highlights.
Medical research is one of the focus areas Personalized medicine And also the use of organoids. For example, in the case of cancer, a biopsy sample of each patient’s tumor has to be taken and the specific organoid produced from it,” says Encabo. In this case, different chemotherapy agents can be tested and checked “very accurately”, as the specialist points out, how they will affect the patient and be most effective in removing the tumor.
At Aragon’s Biobank they have been able to grow organoids from both healthy and tumor tissue from the kidney, colon, breast and central nervous system. But, in addition, they are currently working not only on its development, but also characteristic of these tissues.
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