A novel integrated system using patient-derived glioma cerebral organoids and xenografts for disease modeling and drug screening.

A physiologically relevant glioma tumor model is important to the study of disease progression and screening drug candidates. However, current preclinical glioma models lack the brain microenvironment, and the established tumor cell lines do not represent glioma biology and cannot be used to evaluate the therapeutic effect. Here, we reported a real-time integrated system by generating 3D ex vivo cerebral organoids and in vivo xenograft tumors based on glioma patient-derived tissues and cells. Our system faithfully recapitulated the histological features, response to chemotherapy drugs, and clinical progression of their corresponding parental tumors. Additionally, our model successfully identified a case from a grade II astrocytoma patient with typical grade IV GBM features in both organoids and xenograft models, which mimicked the disease progression of this patient. Further genomic and transcriptomic characterization was associated with individual clinical features. We have demonstrated the "GBM-&Normal-like" signature to predict prognosis. In conclusion, we developed an integrated system of parallel models from patient-derived glioma cerebral organoids and xenografts for understanding the glioma biology and prediction of response to chemotherapy drugs, which might lead to a new strategy for personalized treatment for this deadly disease.

Zhang L ，Liu F ，Weygant N ，Zhang J ，Hu P ，Qin Z ，Yang J ，Cheng Q ，Fan F ，Zeng Y ，Tang Y ，Li Y ，Tang A ，He F ，Peng J ，Liao W ，Hu Z ，Li M ，Liu Z ... -  《-》

Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology.

Golebiewska A ，Hau AC ，Oudin A ，Stieber D ，Yabo YA ，Baus V ，Barthelemy V ，Klein E ，Bougnaud S ，Keunen O ，Wantz M ，Michelucci A ，Neirinckx V ，Muller A ，Kaoma T ，Nazarov PV ，Azuaje F ，De Falco A ，Flies B ，Richart L ，Poovathingal S ，Arns T ，Grzyb K ，Mock A ，Herold-Mende C ，Steino A ，Brown D ，May P ，Miletic H ，Malta TM ，Noushmehr H ，Kwon YJ ，Jahn W ，Klink B ，Tanner G ，Stead LF ，Mittelbronn M ，Skupin A ，Hertel F ，Bjerkvig R ，Niclou SP ... -  《-》

Pancreatic cancer-derived organoids - a disease modeling tool to predict drug response.

Frappart PO ，Walter K ，Gout J ，Beutel AK ，Morawe M ，Arnold F ，Breunig M ，Barth TF ，Marienfeld R ，Schulte L ，Ettrich T ，Hackert T ，Svinarenko M ，Rösler R ，Wiese S ，Wiese H ，Perkhofer L ，Müller M ，Lechel A ，Sainz B Jr ，Hermann PC ，Seufferlein T ，Kleger A ... -  《-》

The generation of glioma organoids and the comparison of two culture methods.

The intra- and inter-tumoral heterogeneity of gliomas and the complex tumor microenvironment make accurate treatment of gliomas challenging. At present, research on gliomas mainly relies on cell lines, stem cell tumor spheres, and xenotransplantation models. The similarity between traditional tumor models and patients with glioma is very low. In this study, we aimed to address the limitations of traditional tumor models by generating patient-derived glioma organoids using two methods that summarized the cell diversity, histological features, gene expression, and mutant profiles of their respective parent tumors and assess the feasibility of organoids for personalized treatment. We compared the organoids generated using two methods through growth analysis, immunohistological analysis, genetic testing, and the establishment of xenograft models. Both types of organoids exhibited rapid infiltration when transplanted into the brains of adult immunodeficient mice. However, organoids formed using the microtumor method demonstrated more similar cellular characteristics and tissue structures to the parent tumors. Furthermore, the microtumor method allowed for faster culture times and more convenient operational procedures compared to the Matrigel method. Patient-derived glioma organoids, especially those generated through the microtumor method, present a promising avenue for personalized treatment strategies. Their capacity to faithfully mimic the cellular and molecular characteristics of gliomas provides a valuable platform for elucidating tumor biology and evaluating therapeutic modalities. The success rates of the Matrigel and microtumor methods were 45.5% and 60.5%, respectively. The microtumor method had a higher success rate, shorter establishment time, more convenient passage and cryopreservation methods, better simulation of the cellular and histological characteristics of the parent tumor, and a high genetic guarantee.

Zhang Y ，Shao Y ，Li Y ，Li X ，Zhang X ，E Q ，Wang W ，Jiang Z ，Gan W ，Huang Y ... -  《Cancer Medicine》

Protocol for derivation of organoids and patient-derived orthotopic xenografts from glioma patient tumors.

Tumor organoids and patient-derived orthotopic xenografts (PDOXs) are some of the most valuable pre-clinical tools in cancer research. In this protocol, we describe efficient derivation of organoids and PDOX models from glioma patient tumors. We provide detailed steps for organoid culture, intracranial implantation, and detection of tumors in the brain. We further present technical adjustments for standardized functional assays and drug testing. For complete details on the use and execution of this protocol, please refer to Golebiewska et al. (2020).

Oudin A ，Baus V ，Barthelemy V ，Fabian C ，Klein E ，Dieterle M ，Wantz M ，Hau AC ，Dording C ，Bernard A ，Michelucci A ，Yabo YA ，Kanli G ，Keunen O ，Bjerkvig R ，Niclou SP ，Golebiewska A ... -  《-》