{"corpus_id":195762529,"paper_sha":"dd66e604ac983bf71609988437c8ef2ec7df1a00","doi":"10.26508/lsa.201900305","arxiv_id":null,"pmid":31249133,"pmcid":"6599970","mag_id":2953470284,"dblp_id":null,"acl_id":null,"title":"Human organotypic brain slice culture: a novel framework for environmental research in neuro-oncology","year":2019,"publication_date":"2019-06-27","venue":"Life Science Alliance","journal":{"name":"Life Science Alliance","pages":null,"volume":"2"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine","Environmental Science"],"reference_count":61,"citation_count":63,"influential_citation_count":2,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Adult","mj":false,"ui":"D000328"},{"d":"Aged","mj":false,"ui":"D000368"},{"d":"Aged, 80 and over","mj":false,"ui":"D000369"},{"d":"Astrocytes","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D001253"},{"d":"Brain","mj":false,"qs":[{"q":"cytology","mj":false,"ui":"Q000166"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"surgery","mj":false,"ui":"Q000601"}],"ui":"D001921"},{"d":"Brain Neoplasms","mj":true,"qs":[{"q":"drug therapy","mj":false,"ui":"Q000188"},{"q":"immunology","mj":false,"ui":"Q000276"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D001932"},{"d":"Cell Movement","mj":false,"ui":"D002465"},{"d":"Cell Proliferation","mj":false,"ui":"D049109"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Glioblastoma","mj":true,"qs":[{"q":"drug therapy","mj":false,"ui":"Q000188"},{"q":"immunology","mj":false,"ui":"Q000276"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D005909"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Infant","mj":false,"ui":"D007223"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Middle Aged","mj":false,"ui":"D008875"},{"d":"Models, Biological","mj":false,"ui":"D008954"},{"d":"Nerve Tissue","mj":false,"qs":[{"q":"cytology","mj":false,"ui":"Q000166"},{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"surgery","mj":false,"ui":"Q000601"}],"ui":"D009417"},{"d":"Temozolomide","mj":false,"qs":[{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D000077204"},{"d":"Tissue Culture Techniques","mj":false,"qs":[{"q":"methods","mj":true,"ui":"Q000379"}],"ui":"D046509"},{"d":"Tumor Microenvironment","mj":false,"ui":"D059016"}],"chemicals":[{"n":"Temozolomide","ui":"D000077204","reg":"YF1K15M17Y"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://www.life-science-alliance.org/content/lsa/2/4/e201900305.full.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/dd66e604ac983bf71609988437c8ef2ec7df1a00","s2_open_access_license":"CCBY","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Therapeutically resected, adult brain segments were maintained and characterized for an extended period to study glioblastoma progression and treatment in its almost natural environment. When it comes to the human brain, models that closely mimic in vivo conditions are lacking. Living neuronal tissue is the closest representation of the in vivo human brain outside of a living person. Here, we present a method that can be used to maintain therapeutically resected healthy neuronal tissue for prolonged periods without any discernible changes in tissue vitality, evidenced by immunohistochemistry, genetic expression, and electrophysiology. This method was then used to assess glioblastoma (GBM) progression in its natural environment by microinjection of patient-derived tumor cells into cultured sections. The result closely resembles the pattern of de novo tumor growth and invasion, drug therapy response, and cytokine environment. Reactive transformation of astrocytes, as an example of the cellular nonmalignant tumor environment, can be accurately simulated with transcriptional differences similar to those of astrocytes isolated from acute GBM specimens. In a nutshell, we present a simple method to study GBM in its physiological environment, from which valuable insights can be gained. This technique can lead to further advancements in neuroscience, neuro-oncology, and pharmacotherapy.","claims":[{"public_id":"cl_01bb7d75d6d31e571e64a1ea47a1e7a5","status":"active","text":"Microinjection of patient-derived tumor cells into cultured sections enables assessment of glioblastoma progression in a natural environment.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_01bb7d75d6d31e571e64a1ea47a1e7a5"},{"public_id":"cl_07f514dec79147e82843c8078421bb90","status":"active","text":"Reactive transformation of astrocytes can be accurately simulated in the slice culture, with transcriptional differences similar to those of astrocytes isolated from acute glioblastoma specimens.","confidence":0.94,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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