Scientists use various models to investigate the biology of healthy tissue and diseases in the laboratory. For example, cell lines, laboratory animals and, for several years now, 3D mini-organs (organoids). These organoids have certain characteristics and are so complex that scientists can accurately mimic an organ's functions in the laboratory. They are therefore used for research purposes, including understanding how cancer can start in a healthy brain, drug sensitivity testing and finding leads for new drugs.
Last year, research group leaders Dr. Benedetta Artegiani, Prof. Dr. Hans Clevers and Dr. Delilah Hendriks shared their revolutionary work to grow 3D mini-organs from human fetal brain tissue in the laboratory. Today in Nature Protocols, Artegiani, Hendriks and their colleagues share the method for growing these brain organoids, termed FeBOs, and then adapting them to model a specific type of brain tumor.
DNA alteration
There are many different types of brain tumors in children, many more than in adults. All of these types are rare, so there is little tumor tissue available to use for research. In the protocol published today, the researchers share how CRISPR/Cas9 technology can be used to modify the DNA of some cells within the starting organoid. Thus, if the DNA profile of the tumor type is known, an organoid of a particular type of brain cancer can be generated from this so-called FeBO.
Anna Pagliaro is a PhD student in the Artegiani & Hendriks group and one of the three first authors of the study. She says: ' One of the strengths of the developed model is that we can investigate how a tumor cell behaves in a healthy environment. This realistic environment makes it possible to investigate, for example, the accelerated growth and behavior of invasion of tumor cells in healthy tissue.'
The modified organoids can also be used to test the sensitivity to various drugs. Francesco Andreatta, PhD student and co-first author: 'By testing different drugs on the organoids and examining cell viability, we can determine how the cancer cells respond, and which drugs are potential leads for treatment.' 'We can also see if certain drugs change the behavior of the organoids. For example, their speed of growth or a change in how the cells are arranged in the organoid,' adds PhD student Roxy Finger and co-first author of the study.
In addition, the organoids will also provide important information about the development of brain cancer. At the molecular level, they can offer insight into the change from a healthy cell to a cancerous cell. By sharing the culture protocols with the scientific community, Artegiani and Hendriks hope to help other researchers accelerate their research into new treatments and the origin of brain tumors.
This publication was made possible in part by Oncode Accelerator. The Oncode Accelerator Project receives funding from the Dutch National Growth Fund (NGF).