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A major obstacle for understanding this tumor\u2010vascular niche is the lack of a perfusable vascular model of DMG. To address this, we have established an in vitro model of the DMG\u2010BBTB, comprised of patient\u2010derived DMG tumor cells and primary human brain microvascular endothelial cells, astrocytes, and vascular pericytes, embedded in a fibrin matrix within a microfluidic chip. We report the development and characterization of self\u2010assembled microvascular networks, with consistent vasculature development across a range of tumor cell densities. Perfusion studies showed no significant alterations in vascular permeability when tumor cells were present. To elucidate transcriptomic changes, we employed scRNAseq on devices containing blood\u2013brain barrier (BBB), DMG\u2010BBTB, or tumor necrosis factor alpha (TNF\u03b1)\u2010stimulated control. We observed significant differential gene expression between BBB and DMG\u2010BBTB, distinct from inflammatory signatures seen with TNF\u03b1 perturbation. Our analysis indicated that DMG cells adopted a mesenchymal\u2010like phenotype, with further in silico studies predicting significant receptor\u2010ligand crosstalk between these cells and endothelium. In summary, we developed a high\u2010fidelity DMG\u2010BBTB model that recapitulates transcriptomic features of patient DMG microvasculature and features perfusable vasculature.<\/jats:p>","DOI":"10.1002\/adhm.71474","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:00:19Z","timestamp":1785301219000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineered Microvascular Model of the Blood\u2013Brain\u2013Tumor Barrier Reveals Endothelial Remodeling in Diffuse Midline Glioma"],"prefix":"10.1002","volume":"15","author":[{"given":"Kimberly R.","family":"Bennett","sequence":"first","affiliation":[{"name":"Harvard\u2010MIT Health Sciences &amp; Technology Massachusetts Institute of Technology  Cambridge Massachusetts USA"},{"name":"Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yann S.","family":"Vanrobaeys","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessy","family":"Teboh","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology  Cambridge Massachusetts USA"},{"name":"Department of Biochemistry Wellesley College  Wellesley Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zakiya","family":"Smith","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology  Cambridge Massachusetts USA"},{"name":"Department of Chemical Engineering Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson","family":"Scott","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Hajal","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering Northeastern University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula T.","family":"Hammond","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology  Cambridge Massachusetts USA"},{"name":"Department of Chemical Engineering Massachusetts Institute of Technology  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9446-1718","authenticated-orcid":false,"given":"Joelle P.","family":"Straehla","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology  Cambridge Massachusetts USA"},{"name":"Ben Towne Center for Childhood Cancer &amp; Blood Disorders Research Seattle Children's Research Institute  Seattle Washington USA"},{"name":"Department of Pediatrics University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab106"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdad040"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2015.00148"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.2176\/nmc.ra.2017\u20100018"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.11.037"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2025.1646641"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010019\u20100205\u2010x"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478\u2010021\u201001243\u20101"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00031"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noae245"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noac079.116"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987\u2010020\u201000198\u20100"},{"key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"0","DOI":"10.1093\/neuonc\/noae064.061","article-title":"DIPG\u201008. 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