Cerebral organoids: emerging ex vivo humanoid models of glioblastoma
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REVIEW
Cerebral organoids: emerging ex vivo humanoid models of glioblastoma Michail‑Dimitrios Papaioannou1,2, Kevin Sangster1,3, Rifat Shahriar Sajid1,3, Ugljesa Djuric1,2 and Phedias Diamandis1,2,3,4*
Abstract Glioblastoma is an aggressive form of brain cancer that has seen only marginal improvements in its bleak survival outlook of 12–15 months over the last forty years. There is therefore an urgent need for the development of advanced drug screening platforms and systems that can better recapitulate glioblastoma’s infiltrative biology, a process largely responsible for its relentless propensity for recurrence and progression. Recent advances in stem cell biology have allowed the generation of artificial tridimensional brain-like tissue termed cerebral organoids. In addition to their potential to model brain development, these reagents are providing much needed synthetic humanoid scaffolds to model glioblastoma’s infiltrative capacity in a faithful and scalable manner. Here, we highlight and review the early breakthroughs in this growing field and discuss its potential future role for glioblastoma research. Keywords: Glioblastoma, Cerebral organoids, Cancer modelling, Cancer discovery Introduction A disease with a dismal prognosis
Glioblastoma multiforme (GBM) is a malignant primary brain tumor with a dismal 5-year survival rate of 5% and median survival of just 14 months [1]. Developments of effective treatments are challenged by GBM’s extensive cellular heterogeneity and its ability to infiltrate into surrounding brain tissue, making complete surgical resection infeasible [2]. The majority of GBM tumors recur, partly hypothesized to be due to the presence of a chemo-resistant stem-cell-like population that repopulates the tumor following therapy [3, 4]. Despite numerous drugs reaching clinical trials, the standard of care for GBM treatment has remained largely unchanged for almost two decades [5]. As such, there has been significant interest in refining and expanding laboratory models of GBM in an effort to better recapitulate its true biology, and in turn, help identify new and more effective *Correspondence: [email protected] 3 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada Full list of author information is available at the end of the article
therapies. Emerging models that combine synthetic tridimensional human neural cultures, known as cerebral organoids, with genetically tagged glioma stem cells have provided new tools for scientists to recapitulate the cellular and molecular heterogeneity of GBM. This includes both its ability to interact and infiltrate within normal brain tissue structures providing an exciting emerging model to study this deadly disease. Here, we compare and contrast this model with traditional systems and explore its complementary value in GBM research and discovery. Traditional models of GBM
Primary GBM cell cultures have been crucial in understanding the biology of this disease by providing a wides
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