Rapid and Efficient Invasion Assay of Glioblastoma in Human Brain Organoids
| Autor: | Mariachiara Buccarelli, Gladiola Goranci-Buzhala, Anand Ramani, Elke Gabriel, Quintino Giorgio D'Alessandris, Roberto Pallini, Lucia Ricci-Vitiani, Aruljothi Mariappan, Jay Gopalakrishnan |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
endocrine system tissue clearing ADAM10 3D human brain organoids Settore MED/27 - NEUROCHIRURGIA iPSCs Biology GBM General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Gentamicin protection assay Glioma medicine Organoid Humans Induced pluripotent stem cell fungi imaging Brain Human brain medicine.disease ADAM10 inhibitor Organoids 030104 developmental biology medicine.anatomical_structure NGLN3 glioma stem cells Cancer research Stem cell Glioblastoma glioma invasion 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports. 31:107738 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2020.107738 |
| Popis: | Glioblastoma (GBM) possesses glioma stem cells (GSCs) that exhibit aggressive invasion behavior in the brain. Current preclinical GBM invasion assays using mouse brain xenografts are time consuming and less efficient. Here, we demonstrate an array of methods that allow rapid and efficient assaying of GSCs invasion in human brain organoids. The assays are versatile to characterize various aspects of GSCs, such as invasion, integration, and interaction with mature neurons of brain organoids. Tissue clearing and quantitative 3D imaging of GSCs in host organoids reveal that invasiveness is inversely correlated with the organoids' age. Importantly, the described invasion assays can distinguish the invasive behaviors of primary and recurrent GSCs. The assays are also amenable to test pharmacological agents. As an example, we show that GI254023X, an inhibitor of ADAM10, could prevent the integration of GSCs into the organoids. |
| Databáze: | OpenAIRE |
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