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Despite its distinct clinical features, GS remains underrepresented in glioma research due to the lack of biologically faithful and experimentally tractable models.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We established patient-derived gliosarcoma organoids (GSOs) from freshly resected tumors using a suspension culture system without enzymatic dissociation. Histological, molecular, and functional properties were evaluated using H&amp;E staining, immunohistochemistry, whole-exome sequencing, 3D invasion assays, and single-cell RNA sequencing (scRNA-seq). Drug response assays were performed using temozolomide and ANA-12 (<jats:italic>NTRK2<\/jats:italic> inhibitor).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>GSOs preserved key histological features, genetic alterations, and tumor microenvironmental cell populations from the original tumors. They stable growth and viability over extended culture periods and maintained integrity following cryopreservation and recovery, supporting their long-term utility. 3D invasion assays further revealed infiltrative behavior, consistent with the aggressive nature of GS. Histological and molecular analyses revealed that GSOs retained glial and mesenchymal differentiation, diverse non-malignant stromal cells, and case-specific somatic alterations. Comparative scRNA-seq revealed distinct transcriptional programs: GSOs were enriched for fibroblast-like and oligodendrocyte progenitor-like states, while glioblastoma organoids (GBOs) displayed astrocyte-like differentiation and high connectivity signatures. Functional assays confirmed consistent sensitivity of GSOs to temozolomide, and selective therapeutic response to <jats:italic>NTRK2<\/jats:italic> inhibition was observed in the GSO harboring an <jats:italic>NTRK2<\/jats:italic> alteration, supporting the utility for genomic-context-guided therapy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Together, GSOs constitute a tractable and translationally relevant model that faithfully reflects the cellular complexity, genetic landscape, and tumor-specific heterogeneity. This model addresses a critical gap in GS biology and supports its integration into precision oncology.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12967-025-06952-y","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T11:42:44Z","timestamp":1755171764000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Tumor microenvironment-preserving gliosarcoma organoids as an in vitro preclinical platform: a comparative analysis with glioblastoma models"],"prefix":"10.1186","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0436-8614","authenticated-orcid":false,"given":"Junseong","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5154-9613","authenticated-orcid":false,"given":"Dokyeong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon-Chun","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minyoung","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songzi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Okcho","family":"Na","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youn Soo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6854-1597","authenticated-orcid":false,"given":"Stephen","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6943-5948","authenticated-orcid":false,"given":"Yeun-Jun","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"6952_CR1","doi-asserted-by":"publisher","first-page":"e70347","DOI":"10.1002\/cam4.70347","volume":"13","author":"S Roohani","year":"2024","unstructured":"Roohani S, Mirwald M, Ehret F, Fink C, Konig L, Striefler JK, et al. 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Annu Rev Biomed Eng. 2025;27:473\u201398.","journal-title":"Annu Rev Biomed Eng"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-025-06952-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-025-06952-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-025-06952-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T22:29:47Z","timestamp":1757456987000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/s12967-025-06952-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,14]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["6952"],"URL":"https:\/\/doi.org\/10.1186\/s12967-025-06952-y","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,14]]},"assertion":[{"value":"31 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted in accordance with the principles outlined in the Declaration of Helsinki and received approval from the Institutional Review Board of Seoul St. Mary\u2019s Hospital (Approval Number: KC21TISI0793). Tumor samples were obtained after acquiring informed consent from all participating patients.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"915"}}