journal article·2025-11Open access

Novel Diffuse Midline Glioma‐on‐Chip Recapitulating Tumor Biophysical Microenvironment to Assess the Heterogeneity of Response to Therapies

Lisa Terrassoux, Calypso Hazard, Agathe Laratte, Joanne Balsamelli, Mélanie Arcicasa, Elisa Fong, Léo Baland, Fabrice Soncin, Giovanni Cappello, Claude‐Alain Maurage, Sebastien Janel, Antony Bazir, Fabrizio Cleri, Anthony Treizebre, Eric Lartigau, Yousr Rekik, Samuel Meignan, Alessandro Furlan

Small· Volume 21· Issue 45

Abstract

Abstract Despite significant efforts, Diffuse Midline Gliomas (DMGs) remain incurable. Although promising results are obtained in preclinical studies, most approaches have failed to improve survival in these young patients. In this context, by integrating elements of the biophysical tumor microenvironment known to regulate the response to therapies, a new preclinical tool is developed to better evaluate the efficacy of antitumoral strategies. For this purpose, a novel DMG‐on‐Chip (DoC) is engineered composed of a 3D dense tumor disk embedded in an extracellular matrix, which is accessible for real‐time monitoring using wide‐field phase contrast or confocal fluorescence microscopy. By driving the oxygen supply within the chip solely in a radial manner, a hypoxia gradient is established that can be associated with changes in DMG cell phenotype, proliferation, and rewiring of metabolic and stress transcriptomic signatures. Finally, DoC is used to analyze the spatial heterogeneity of the response of DMG cell lines and patient‐derived 3D cultures to treatments through cell segmentation. Altogether, these interdisciplinary characterizations validate the new tool as an interesting healthcare solution to understand how cell responses are modulated by biophysical or biochemical cues in the tumor microenvironment.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: 3D Printing in Biomedical Research · Glioma Diagnosis and Treatment · Nanoplatforms for cancer theranostics

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Université Lille CNRS Inserm CHU Lille UMR9020‐U1277‐CANTHER‐Cancer Heterogeneity Plasticity and Resistance to Therapies Lille F‐59000 France

Tumorigenesis and Resistance to Treatment Unit Centre Oscar Lambret Lille F‐59000 France

CNRS/IIS/Centre Oscar Lambret/Lille University SMMiL‐E Project CNRS Délégation Hauts‐de‐France 43 Avenue le Corbusier Lille 59800 France

CNRS IRL2820 Laboratory for Integrated Micro Mechatronic Systems Institute of Industrial Science University of Tokyo 4‐6‐1 Komaba, Meguro‐ku Tokyo 153‐8505 Japan

Laboratory of Interdisciplinary Physics (LIPhy) University Grenoble Alpes, CNRS Grenoble F‐38000 France

Institut de Pathologie CHU Lille Lille 59000 France

Université de Lille CNRS Inserm CHU Lille Institut Pasteur de Lille U1019‐UMR9017 CIIL‐Center for Infection and Immunity of Lille Lille F‐59000 France

Université Lille Département de Physique and CNRS UMR 8520‐IEMN‐Institut d'Electronique Microélectronique et Nanotechnologie Villeneuve d'Ascq 59659 France

Université de Lille CNRS Centrale Lille Univ. Polytechnique Hauts‐de‐France UMR 8520‐IEMN‐Institut d'Electronique de Microélectronique et de Nanotechnologie Lille 59000 France

Oscar Lambret Center Academic Radiation Oncology Department Lille 59000 France

Funding

Agence Nationale de la Recherche · Ligue Contre le Cancer · Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'Adolescent · Institut National Du Cancer

References (79)

Show source-provided references
1. 10.1051/medsci/202027910.1051/medsci/2020279 ↗
2. 10.1038/nature1083310.1038/nature10833 ↗
3. 10.1038/ng.110210.1038/ng.1102 ↗
4. 10.1126/science.123224510.1126/science.1232245 ↗
5. 10.1038/nm.385510.1038/nm.3855 ↗
6. 10.1016/j.ccell.2017.03.01110.1016/j.ccell.2017.03.011 ↗
7. 10.1093/neuonc/noad14110.1093/neuonc/noad141 ↗
8. 10.1016/j.semcancer.2023.11.00610.1016/j.semcancer.2023.11.006 ↗
9. 10.1038/s41392-023-01332-810.1038/s41392-023-01332-8 ↗
10. 10.1007/s11060-015-1726-010.1007/s11060-015-1726-0 ↗
11. 10.3390/cancers1112187510.3390/cancers11121875 ↗
12. 10.1016/j.ccell.2020.07.00810.1016/j.ccell.2020.07.008 ↗
13. 10.1158/0008-5472.CAN-23-018610.1158/0008-5472.CAN-23-0186 ↗
14. 10.1158/2159-8290.CD-23-013110.1158/2159-8290.CD-23-0131 ↗
15. 10.1242/jcs.26172310.1242/jcs.261723 ↗
16. 10.1016/j.ccr.2005.08.01010.1016/j.ccr.2005.08.010 ↗
17. 10.3389/fbioe.2019.0034110.3389/fbioe.2019.00341 ↗
18. 10.1089/ten.tea.2021.011710.1089/ten.tea.2021.0117 ↗
19. 10.1002/(SICI)1097-0215(19980316)75:6<864::AID-IJC8>3.0.CO;2-T10.1002/(SICI)1097-0215(19980316)75:6<864::AID-IJC8>3.0.CO;2-T ↗
20. 10.1007/s10048-024-00763-x10.1007/s10048-024-00763-x ↗
21. 10.1186/s40478-024-01765-410.1186/s40478-024-01765-4 ↗
22. 10.1002/adma.20230069210.1002/adma.202300692 ↗
23. 10.1002/smll.20230852510.1002/smll.202308525 ↗
24. 10.3390/cancers1419458110.3390/cancers14194581 ↗
25. 10.1038/s41568-023-00593-310.1038/s41568-023-00593-3 ↗
26. 10.1038/s41551-019-0363-x10.1038/s41551-019-0363-x ↗
27. 10.1088/2050-6120/1/4/04500210.1088/2050-6120/1/4/045002 ↗
28. 10.1073/pnas.100694510810.1073/pnas.1006945108 ↗
29. 10.1140/epje/i2019-11878-710.1140/epje/i2019-11878-7 ↗
30. 10.1093/neuonc/noz14010.1093/neuonc/noz140 ↗
31. 10.1177/0271678X1664309010.1177/0271678X16643090 ↗
32. 10.1038/s41598-018-35679-810.1038/s41598-018-35679-8 ↗
33. 10.1371/journal.pcbi.100646910.1371/journal.pcbi.1006469 ↗
34. 10.1007/s10544-013-9808-210.1007/s10544-013-9808-2 ↗
35. 10.1038/ncomms1405610.1038/ncomms14056 ↗
36. 10.1007/s00418-020-01857-x10.1007/s00418-020-01857-x ↗
37. 10.1038/s41586-024-08452-310.1038/s41586-024-08452-3 ↗
38. 10.1016/j.ccell.2017.08.01710.1016/j.ccell.2017.08.017 ↗
39. 10.3390/cancers1321555110.3390/cancers13215551 ↗
40. 10.1016/j.trecan.2023.02.00310.1016/j.trecan.2023.02.003 ↗
41. 10.1038/s41551-020-00621-910.1038/s41551-020-00621-9 ↗
42. 10.1016/j.biomaterials.2018.01.05310.1016/j.biomaterials.2018.01.053 ↗
43. 10.7554/eLife.6325810.7554/eLife.63258 ↗
44. 10.1007/s00234-024-03491-z10.1007/s00234-024-03491-z ↗
45. 10.1038/s41598-023-39277-110.1038/s41598-023-39277-1 ↗
46. 10.1038/s41467-020-17245-x10.1038/s41467-020-17245-x ↗
47. 10.1186/s40170-021-00257-610.1186/s40170-021-00257-6 ↗
48. 10.2147/HP.S9219810.2147/HP.S92198 ↗
49. 10.1093/neuonc/noae25510.1093/neuonc/noae255 ↗
50. Voskuil F. J. · SHINE study group Nat. Commun. · 2020 · 11 · 3257
51. 10.1158/1078-0432.CCR-19-012610.1158/1078-0432.CCR-19-0126 ↗
52. 10.1016/j.ejca.2024.11516510.1016/j.ejca.2024.115165 ↗
53. 10.1016/j.neo.2023.10089610.1016/j.neo.2023.100896 ↗
54. 10.3389/fendo.2021.74221510.3389/fendo.2021.742215 ↗
55. 10.1126/sciimmunol.ade568610.1126/sciimmunol.ade5686 ↗
56. 10.1002/eji.20225025810.1002/eji.202250258 ↗
57. 10.1002/smll.20230142010.1002/smll.202301420 ↗
58. 10.1038/s41588-022-01236-310.1038/s41588-022-01236-3 ↗
59. 10.1038/s41467-024-52096-w10.1038/s41467-024-52096-w ↗
60. 10.1016/j.ccell.2023.09.00110.1016/j.ccell.2023.09.001 ↗
61. 10.1038/s41586-022-04489-410.1038/s41586-022-04489-4 ↗
62. du Chatinier A. · Neurooncol Adv · 2022 · 4
63. 10.1093/neuonc/noae24510.1093/neuonc/noae245 ↗
64. 10.1038/s41586-024-08579-310.1038/s41586-024-08579-3 ↗
65. 10.3390/pharmaceutics1205039910.3390/pharmaceutics12050399 ↗
66. 10.1186/s12987-020-00198-010.1186/s12987-020-00198-0 ↗
67. 10.1038/s41592-022-01507-110.1038/s41592-022-01507-1 ↗
68. R.Haase G.Witz M.Fernandes M. L.Zoccoler S.Taylor M.Lampert T.Korten haesleinhuepf/BioImageAnalysisNotebooks: gpt‐2024.1.6 2024.
69. 10.1093/bioinformatics/btz93110.1093/bioinformatics/btz931 ↗
70. 10.1073/pnas.050658010210.1073/pnas.0506580102 ↗
71. 10.1038/s41598-017-05383-010.1038/s41598-017-05383-0 ↗
72. 10.1039/C8NR08955H10.1039/C8NR08955H ↗
73. 10.1023/A:101192700430710.1023/A:1011927004307 ↗
74. 10.1038/nrc107510.1038/nrc1075 ↗
75. 10.1039/D1AN00817J10.1039/D1AN00817J ↗
76. 10.1259/bjr.2013067610.1259/bjr.20130676 ↗
77. 10.1016/j.cmet.2006.01.01210.1016/j.cmet.2006.01.012 ↗
78. 10.1371/journal.pcbi.100796110.1371/journal.pcbi.1007961 ↗
79. 10.1371/journal.pcbi.100441210.1371/journal.pcbi.1004412 ↗