Abstract
Although meningioma is the most common primary brain tumor, treatments depend only on the surgery and radiotherapy, and recurrent meningiomas have no standard therapeutic options due to a lack of clinically relevant research models. Current meningioma cell lines or organoids cannot reflect biological features of patients’ tumors since they undergo transformation along culture and consist of only tumor cells without microenvironment. Here, we firstly established patient-derived meningioma organoids (MNOs) preserving diverse cell types of tumor microenvironment, including endothelial cells and macrophage/microglia cells. Exclusion of the enzymatic dissociation-reaggregation steps endowed MNOs with original histology and tumor microenvironment. In addition, we used liquid media culture system instead of embedding into Matrigel, thus easy-to-handle, cost-efficient, and time-saving. MNOs maintained their functionality and morphology after long-term culture ( > 9 wk) and repeated cryopreserving-recovery cycles. The similarity between MNOs and their corresponding parental tumors were confirmed by both immunohistochemistry and whole-exome sequencing. As a representative application, we utilized MNOs in drug screening, and mifepristone, an antagonist of progesterone receptor, showed prominent antitumor efficacy in respect to viability, invasiveness, and protein expression. Taken together, our MNO model overcame limitations of previous meningioma models and showed superiority in terms of resemblance with parental tumors. Thus, we expect that our model can facilitate translational research of identifying and selecting drugs for meningioma in the era of precision medicine.