eprintid: 10135584 rev_number: 12 eprint_status: archive userid: 608 dir: disk0/10/13/55/84 datestamp: 2021-10-04 11:41:01 lastmod: 2021-10-04 11:41:01 status_changed: 2021-10-04 11:41:01 type: article metadata_visibility: show creators_name: Osuna de la Peña, D creators_name: Trabulo, SMD creators_name: Collin, E creators_name: Liu, Y creators_name: Sharma, S creators_name: Tatari, M creators_name: Behrens, D creators_name: Erkan, M creators_name: Lawlor, RT creators_name: Scarpa, A creators_name: Heeschen, C creators_name: Mata, A creators_name: Loessner, D title: Bioengineered 3D models of human pancreatic cancer recapitulate in vivo tumour biology ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: K71 note: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. abstract: Patient-derived in vivo models of human cancer have become a reality, yet their turnaround time is inadequate for clinical applications. Therefore, tailored ex vivo models that faithfully recapitulate in vivo tumour biology are urgently needed. These may especially benefit the management of pancreatic ductal adenocarcinoma (PDAC), where therapy failure has been ascribed to its high cancer stem cell (CSC) content and high density of stromal cells and extracellular matrix (ECM). To date, these features are only partially reproduced ex vivo using organoid and sphere cultures. We have now developed a more comprehensive and highly tuneable ex vivo model of PDAC based on the 3D co-assembly of peptide amphiphiles (PAs) with custom ECM components (PA-ECM). These cultures maintain patient-specific transcriptional profiles and exhibit CSC functionality, including strong in vivo tumourigenicity. User-defined modification of the system enables control over niche-dependent phenotypes such as epithelial-to-mesenchymal transition and matrix deposition. Indeed, proteomic analysis of these cultures reveals improved matrisome recapitulation compared to organoids. Most importantly, patient-specific in vivo drug responses are better reproduced in self-assembled cultures than in other models. These findings support the use of tuneable self-assembling platforms in cancer research and pave the way for future precision medicine approaches. date: 2021-09-24 date_type: published official_url: https://doi.org/10.1038/s41467-021-25921-9 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1890113 doi: 10.1038/s41467-021-25921-9 pii: 10.1038/s41467-021-25921-9 lyricists_name: Osuna de la Pena, David lyricists_id: DOSUN94 actors_name: Osuna de la Pena, David actors_id: DOSUN94 actors_role: owner full_text_status: public publication: Nature Communications volume: 12 article_number: 5623 event_location: England issn: 2041-1723 citation: Osuna de la Peña, D; Trabulo, SMD; Collin, E; Liu, Y; Sharma, S; Tatari, M; Behrens, D; ... Loessner, D; + view all <#> Osuna de la Peña, D; Trabulo, SMD; Collin, E; Liu, Y; Sharma, S; Tatari, M; Behrens, D; Erkan, M; Lawlor, RT; Scarpa, A; Heeschen, C; Mata, A; Loessner, D; - view fewer <#> (2021) Bioengineered 3D models of human pancreatic cancer recapitulate in vivo tumour biology. Nature Communications , 12 , Article 5623. 10.1038/s41467-021-25921-9 <https://doi.org/10.1038/s41467-021-25921-9>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10135584/1/Osuna%20de%20la%20Pe%C3%B1a%20et%20al.%20-%202021%20-%20Bioengineered%203D%20models%20of%20human%20pancreatic%20cancer%20recapitulate%20in%20vivo%20tumour%20biology.pdf