Brain tumor "in vitro"
Glioblastoma learned to grow on the "minimozg"
Studies of an aggressive brain tumor – glioblastoma – used to be very difficult, since scientists could not grow a culture of tumor cells in the laboratory, and the results obtained in animal experiments are not always fully applied to humans. Therefore, many questions about the molecular processes associated with the growth and development of this tumor remained unanswered. Now scientists from the Salk Institute have managed to solve this problem. By editing just two genes, they reproduced glioblastoma in cerebral organoids – miniature brain likenesses from human cells that are grown in Petri dishes.
Scientists have begun to create primitive miniature analogues of various organs from cell cultures in recent years. Organoids of the kidney, intestine, liver, lung, breast, prostate were obtained, and in 2011 Madeleine Lancaster managed to create a miniature brain in a laboratory in Vienna.
In the current study, the organoids were three-dimensional structures of cells, about four millimeters in size. Using the CRISPR-Cas9 method, scientists modified two genes, HRas and p53, which, as previously established, are associated with glioblastoma. In the normal case, HRas activates cell growth, and p53 inhibits this process. If the first of the genes works at full power, and the second does not function, a tumor occurs. Genome modification was carried out only in a few cells of the organoid. As a result, tumor-like structures appeared in the organoids, which grew rapidly and eventually captured the entire organoid, replacing healthy cells. They contained a number of biomarkers characteristic of glioblastoma.
From left to right: tumor cells marked with the red fluorescent marker tdTomato spread in the brain organoid during 2, 3, 4, 6, 8, 10 and 13 weeks after transduction. A drawing from the press release of the Salk Institute Organoids reveal how a deadly brain cancer grows – VM.
It is convenient to transplant such organoids to laboratory animals, initiating the development of a tumor. Also, using the fluorescent protein gene linked to the modified HRas gene, it is possible to easily track the spread of tumor cells inside the organoid. The resulting model will now allow not only to study in more detail how this dangerous tumor grows, but also to test new drugs in the laboratory. It will also be possible to conduct personalized therapy, studying how a tumor reacts to various drugs, the genome of which exactly corresponds to the genome of a particular patient's tumor.
Article by Ogawa et al. Glioblastoma Model Using Human Cerebral Organoids is published in the journal Cell Reports.
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