{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:59:26Z","timestamp":1790096366843,"version":"4.0.1"},"reference-count":96,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T00:00:00Z","timestamp":1730937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["2020R1A2C1012564"],"award-info":[{"award-number":["2020R1A2C1012564"]}]},{"name":"National Research Foundation of Korea (NRF)","award":["RS-2023-00218543"],"award-info":[{"award-number":["RS-2023-00218543"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biosensors"],"abstract":"<jats:p>Glioblastoma multiforme (GBM) is among the most aggressive brain cancers, and it contains glioma stem cells (GSCs) that drive tumor initiation, progression, and recurrence. These cells resist conventional therapies, contributing to high recurrence rates in GBM patients. Developing in vitro models that mimic the tumor microenvironment (TME), particularly the GSC niche, is crucial for understanding GBM growth and therapeutic resistance. Three-dimensional (3D) spheroid models provide a more physiologically relevant approach than traditional two-dimensional (2D) cultures, recapitulating key tumor features like hypoxia, cell heterogeneity, and drug resistance. This review examines scaffold-free and scaffold-based methods for generating 3D GBM spheroids, focusing on their applications in studying the cancer stem cell niche. The discussion encompasses methods such as the hanging drop, low-adhesion plates, and magnetic levitation, alongside advancements in embedding spheroids within extracellular matrix-based hydrogels and employing 3D bioprinting to fabricate more intricate tumor models. These 3D culture systems offer substantial potential for enhancing our understanding of GBM biology and devising more effective targeted therapies.<\/jats:p>","DOI":"10.3390\/bios14110539","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T06:41:22Z","timestamp":1730961682000},"page":"539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Recapitulating Glioma Stem Cell Niches Using 3D Spheroid Models for Glioblastoma Research"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0957-4345","authenticated-orcid":false,"given":"Hyunji","family":"Jo","sequence":"first","affiliation":[{"name":"Department of Metabiohealth, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3140-4384","authenticated-orcid":false,"given":"Seulgi","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Metabiohealth, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8867-9764","authenticated-orcid":false,"given":"Min-Hyeok","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Mechanical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3062-1302","authenticated-orcid":false,"given":"Sungsu","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Metabiohealth, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea"},{"name":"School of Mechanical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea"},{"name":"Department of Quantum Biophysics, Institute of Quantum Biophysics (IQB), Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea"},{"name":"Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2503-1204","authenticated-orcid":false,"given":"Seo-Yeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Wonkwang University School of Medicine, Iksan 54538, Republic of Korea"},{"name":"Department of Biomedical Science, Wonkwang University School of Medicine, Iksan 54538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Di Nunno, V., Franceschi, E., Tosoni, A., Gatto, L., Bartolini, S., and Brandes, A.A. 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