Academic Bibliography
https://biblio.ugent.be/
Ghent University Academic Bibliography2000-01-01T00:00+00:001monthlyA preclinical platform for assessing long-term drug efficacy exploiting mechanically tunable scaffolds colonized by a three-dimensional tumor microenvironment.
https://biblio.ugent.be/publication/01HSZQ9YT009G32H38JJJHKH6Q
De Vlieghere, EllyVan de Vijver, KoenBlondeel, EvaCarpentier, NathanGhobeira, RoubaPauwels, JarneRiemann, SebastianMinsart, ManonFieuws, CharlotteMestach, JohannaBaeyens, AnsDe Geyter, NathalieDebbaut, CharlotteDenys, HanneloreDescamps, BenedicteClaes, KathleenVral, AnneVan Dorpe, JoGevaert, KrisDe Geest, BrunoCeelen, WimVan Vlierberghe, SandraDe Wever, Olivier2023<h4>Background</h4>Long-term drug evaluation heavily relies upon rodent models. Drug discovery methods to reduce animal models in oncology may include three-dimensional (3D) cellular systems that take into account tumor microenvironment (TME) cell types and biomechanical properties.<h4>Methods</h4>In this study we reconstructed a 3D tumor using an elastic polymer (acrylate-endcapped urethane-based poly(ethylene glycol) (AUPPEG)) with clinical relevant stiffness. Single cell suspensions from low-grade serous ovarian cancer (LGSOC) patient-derived early passage cultures of cancer cells and cancer-associated fibroblasts (CAF) embedded in a collagen gel were introduced to the AUPPEG scaffold. After self-organization in to a 3D tumor, this model was evaluated by a long-term (> 40 days) exposure to a drug combination of MEK and HSP90 inhibitors. The drug-response results from this long-term in vitro model are compared with drug responses in an orthotopic LGSOC xenograft mouse model.<h4>Results</h4>The in vitro 3D scaffold LGSOC model mimics the growth ratio and spatial organization of the LGSOC. The AUPPEG scaffold approach allows to test new targeted treatments and monitor long-term drug responses. The results correlate with those of the orthotopic LGSOC xenograft mouse model.<h4>Conclusions</h4>The mechanically-tunable scaffolds colonized by a three-dimensional LGSOC allow long-term drug evaluation and can be considered as a valid alternative to reduce, replace and refine animal models in drug discovery.application/pdfhttps://biblio.ugent.be/publication/01HSZQ9YT009G32H38JJJHKH6Qhttp://hdl.handle.net/1854/LU-01HSZQ9YT009G32H38JJJHKH6Qhttp://doi.org/10.1186/s40824-023-00441-3https://biblio.ugent.be/publication/01HSZQ9YT009G32H38JJJHKH6Q/file/01HSZQCFXNDZZAGWH2DJ6MHVWQengNo license (in copyright)info:eu-repo/semantics/openAccessBiomaterials researchISSN: 1226-4601ISSN: 2055-7124A preclinical platform for assessing long-term drug efficacy exploiting mechanically tunable scaffolds colonized by a three-dimensional tumor microenvironment.journalArticleinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionGelatin-based hybrid hydrogels as matrices for organoid culture
https://biblio.ugent.be/publication/01HKW42ERDK34FJMR5ENVRGRVC
Carpentier, NathanYe, ShichengDelemarre, Maarten D.Van der Meeren, LouisSkirtach, Andrevan der Laan, Luc J. W.Schneeberger, KerstinSpee, BartDubruel, PeterVan Vlierberghe, Sandra2024The application of liver organoids is very promising in the field of liver tissue engineering; however, it is still facing some limitations. One of the current major limitations is the matrix in which they are cultured. The mainly undefined and murine-originated tumor matrices derived from Engelbreth–Holm–Swarm (EHS) sarcoma, such as Matrigel, are still the standard culturing matrices for expansion and differentiation of organoids toward hepatocyte-like cells, which will obstruct its future clinical application potential. In this study, we exploited the use of newly developed highly defined hydrogels as potential matrices for the culture of liver organoids and compared them to Matrigel and two hydrogels that were already researched in the field of organoid research [i.e., polyisocyanopeptides, enriched with laminin–entactin complex (PIC-LEC) and gelatin methacryloyl (GelMA)]. The newly developed hydrogels are materials that have a physicochemical resemblance with native liver tissue. Norbornene-modified dextran cross-linked with thiolated gelatin (DexNB-GelSH) has a swelling ratio and macro- and microscale properties that highly mimic liver tissue. Norbornene-modified chondroitin sulfate cross-linked with thiolated gelatin (CSNB-GelSH) contains chondroitin sulfate, which is a glycosaminoglycan (GAG) that is present in the liver ECM. Furthermore, CSNB-GelSH hydrogels with different mechanical properties were evaluated. Bipotent intrahepatic cholangiocyte organoids (ICOs) were applied in this work and encapsulated in these materials. This research revealed that the newly developed materials outperformed Matrigel, PIC-LEC, and GelMA in the differentiation of ICOs toward hepatocyte-like cells. Furthermore, some trends indicate that an interplay of both the chemical composition and the mechanical properties has an influence on the relative expression of certain hepatocyte markers. Both DexNB-GelSH and CSNB-GelSH showed promising results for the expansion and differentiation of intrahepatic cholangiocyte organoids. The stiffest CSNB-GelSH hydrogel even significantly outperformed Matrigel based on ALB, BSEP, and CYP3A4 gene expression, being three important hepatocyte markers.application/pdfhttps://biblio.ugent.be/publication/01HKW42ERDK34FJMR5ENVRGRVChttp://hdl.handle.net/1854/LU-01HKW42ERDK34FJMR5ENVRGRVChttp://doi.org/10.1021/acs.biomac.2c01496https://biblio.ugent.be/publication/01HKW42ERDK34FJMR5ENVRGRVC/file/01HQ5KN7QQKYBDBYXRMX9BYGRNengNo license (in copyright)info:eu-repo/semantics/restrictedAccessBIOMACROMOLECULESISSN: 1525-7797ISSN: 1526-4602ChemistryMaterials ChemistryPolymers and PlasticsBiomaterialsBioengineeringSTEM-CELLSLIVERGelatin-based hybrid hydrogels as matrices for organoid culturejournalArticleinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion