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

Yang Zhang, Yunxiang Shao,Yanyan Li, Xuetao Li,Xuewen Zhang, Qinzhi E, Weichao Wang, Zuoyu Jiang,Wenjuan Gan,Yulun Huang

CANCER MEDICINE(2024)

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摘要
BackgroundThe 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.AimsIn 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.Materials and MethodsWe compared the organoids generated using two methods through growth analysis, immunohistological analysis, genetic testing, and the establishment of xenograft models.ResultsBoth 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.DiscussionPatient-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.ConclusionThe 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. Organoids can be produced rapidly, frozen, and resuscitated directly. Organoids exhibit rapid infiltration when transplanted in mice brains. Organoids can be rapidly established and used for personalized patient treatment.image
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关键词
glioma,organoid,patient-derived orthotopic xenograft model,stem cell
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