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Because GSCs resist conventional surgery, radiotherapy, and temozolomide, recurrence remains common. This review focuses on in vitro models that mimic the tumor microenvironment, especially the GSC niche. It evaluates 3D spheroid systems as more physiologically relevant than 2D cultures, highlighting scaffold-free and scaffold-based generation methods for studying hypoxia, heterogeneity, and drug resistance.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/recapitulating-glioma-stem-cell-niches-using-3d-spheroid-models-for-glioblastoma-research/332800/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/recapitulating-glioma-stem-cell-niches-using-3d-spheroid-models-for-glioblastoma-research/332800.png","ImageObject",300,407,{"name":92,"@type":93},"Seraphina","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",14,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"Why are glioma stem cells (GSCs) important in glioblastoma multiforme (GBM)?","Question",{"text":113,"@type":114},"GSCs drive GBM initiation, progression, and recurrence and persist after conventional therapies. Their self-renewal, differentiation, and tumor-regenerative abilities contribute to treatment resistance.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What makes 3D spheroid models more useful than traditional 2D cultures for GBM research?",{"text":118,"@type":114},"3D spheroids better recapitulate in vivo tumor features, including hypoxia, cellular heterogeneity, and drug resistance. They provide a more physiologically relevant platform for studying GBM biology.",{"name":120,"@type":111,"acceptedAnswer":121},"What methods are discussed for generating 3D GBM spheroids?",{"text":122,"@type":114},"The review covers scaffold-free and scaffold-based approaches, including hanging drop, low-adhesion plates, and magnetic levitation. It also addresses embedding spheroids in extracellular matrix-based hydrogels and using 3D bioprinting to build more complex tumor models.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},332800,1790126556,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146,"preview_page_count":4},962075114101,"https://ap-avatar.wpscdn.com/avatar/e000253a75eb197efd?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780044092746381165","Review  \nRecapitulating Glioma Stem Cell Niches Using 3D Spheroid Models for Glioblastoma Research  \nHyunji Jo 1,†, Seulgi Lee 1,†, Min-Hyeok Kim 2, Sungsu Park 1,2,3,4, * and Seo-Yeon Lee 5,6, *  \nCitation: Jo, H.; Lee, S.; Kim, M.-H.; Park, S.; Lee, S.-Y. Recapitulating Glioma Stem Cell Niches Using 3D Spheroid Models for Glioblastoma Research. Biosensors 2024, 14, 539 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)bios14110539  \nReceived: 30 September 2024  \nRevised: 29 October 2024  \nAccepted: 5 November 2024  \nPublished: 7 November 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Metabiohealth, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea; [guswl5425@g.skku.edu](guswl5425@g.skku.edu) (H.J.); [tmfrlckdrjs@g.skku.edu](tmfrlckdrjs@g.skku.edu) (S.L.)  \n2 School of Mechanical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea; [mhkim967@g.skku.edu](mhkim967@g.skku.edu)  \n3 Department of Quantum Biophysics, Institute of Quantum Biophysics (IQB), Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea  \n4 Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea  \n5 Department of Pharmacology, Wonkwang University School of Medicine, Iksan 54538, Republic of Korea  \n6 Department of Biomedical Science, Wonkwang University School of Medicine, Iksan 54538, Republic of Korea  \n* [Correspondence: nanopark@skku.edu](Correspondence: nanopark@skku.edu) (S.P.); [brainsw38@wku.ac.kr](brainsw38@wku.ac.kr) (S.-Y.L.); Tel.: +82-31-290-7431 (S.P.);+82-63-850-6773 (S.-Y.L.)  \n† These authors contributed equally to this work.  \nAbstract: 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.  \nKeywords: glioblastoma; glioma stem cells; 3D spheroid; heterogeneity; drug resistance  \n1. Introduction  \nGlioma stem cells (GSCs), a subpopulation with stem cell-like properties, are believed to drive glioblastoma multiforme (GBM) initiation, progression, and recurrence [1,2] . Despite the standard treatment—surgical resection followed by radiotherapy and temozolomide chemotherapy—GBM patients have a median survival of 6 months post-surgery and only 14–16 months with these therapies [3–5] . The high recurrence rate is mainly due to the persistence of GSCs, which resist conventional treatments. These cells exhibit self-renewal, differentiation, and tumor-regenerative abilities, contributing to tumor development, progre","cbCaisF7ZYMfHuGT","https://ap.wps.com/l/cbCaisF7ZYMfHuGT","pdf",5664034,21,"English","# Introduction\n## GSCs and GBM background\n# GSC Niche in GBM\n## Roles and therapy resistance mechanisms\n# 3D Spheroid Models in GBM Research\n## Scaffold-free and scaffold-based spheroid generation","[{\"question\":\"Why are glioma stem cells (GSCs) important in glioblastoma multiforme (GBM)?\",\"answer\":\"GSCs drive GBM initiation, progression, and recurrence and persist after conventional therapies. Their self-renewal, differentiation, and tumor-regenerative abilities contribute to treatment resistance.\"},{\"question\":\"What makes 3D spheroid models more useful than traditional 2D cultures for GBM research?\",\"answer\":\"3D spheroids better recapitulate in vivo tumor features, including hypoxia, cellular heterogeneity, and drug resistance. They provide a more physiologically relevant platform for studying GBM biology.\"},{\"question\":\"What methods are discussed for generating 3D GBM spheroids?\",\"answer\":\"The review covers scaffold-free and scaffold-based approaches, including hanging drop, low-adhesion plates, and magnetic levitation. It also addresses embedding spheroids in extracellular matrix-based hydrogels and using 3D bioprinting to build more complex tumor models.\"}]","Recapitulating Glioma Stem Cell Niches Using 3D Spheroid Models for Glioblastoma Research | PDF",1789999535,53]