Bioprinted cancer model of neuroblastoma in a renal microenvironment as an efficiently applicable drug testing platform

dc.contributor.authorWu, Dongwei
dc.contributor.authorBerg, Johanna
dc.contributor.authorArlt, Birte
dc.contributor.authorRöhrs, Viola
dc.contributor.authorAl-Zeer, Munir A.
dc.contributor.authorDeubzer, Hedwig E.
dc.contributor.authorKurreck, Jens
dc.date.accessioned2022-04-13T13:10:18Z
dc.date.available2022-04-13T13:10:18Z
dc.date.issued2021-12-23
dc.description.abstractDevelopment of new anticancer drugs with currently available animal models is hampered by the fact that human cancer cells are embedded in an animal-derived environment. Neuroblastoma is the most common extracranial solid malignancy of childhood. Major obstacles include managing chemotherapy-resistant relapses and resistance to induction therapy, leading to early death in very-high-risk patients. Here, we present a three-dimensional (3D) model for neuroblastoma composed of IMR-32 cells with amplified genes of the myelocytomatosis viral related oncogene MYCN and the anaplastic lymphoma kinase (ALK) in a renal environment of exclusively human origin, made of human embryonic kidney 293 cells and primary human kidney fibroblasts. The model was produced with two pneumatic extrusion printheads using a commercially available bioprinter. Two drugs were exemplarily tested in this model: While the histone deacetylase inhibitor panobinostat selectively killed the cancer cells by apoptosis induction but did not affect renal cells in the therapeutically effective concentration range, the peptidyl nucleoside antibiotic blasticidin induced cell death in both cell types. Importantly, differences in sensitivity between two-dimensional (2D) and 3D cultures were cell-type specific, making the therapeutic window broader in the bioprinted model and demonstrating the value of studying anticancer drugs in human 3D models. Altogether, this cancer model allows testing cytotoxicity and tumor selectivity of new anticancer drugs, and the open scaffold design enables the free exchange of tumor and microenvironment by any cell type.en
dc.description.sponsorshipDFG, 414044773, Open Access Publizieren 2021 - 2022 / Technische Universität Berlinen
dc.identifier.eissn1422-0067
dc.identifier.issn1661-6596
dc.identifier.urihttps://depositonce.tu-berlin.de/handle/11303/16722
dc.identifier.urihttp://dx.doi.org/10.14279/depositonce-15500
dc.language.isoenen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subject.ddc540 Chemie und zugeordnete Wissenschaftende
dc.subject.otherbioprintingen
dc.subject.othercancer modelen
dc.subject.otherdrug testingen
dc.subject.otherneuroblastomaen
dc.subject.otherpanobinostaten
dc.titleBioprinted cancer model of neuroblastoma in a renal microenvironment as an efficiently applicable drug testing platformen
dc.typeArticleen
dc.type.versionpublishedVersionen
dcterms.bibliographicCitation.articlenumber122en
dcterms.bibliographicCitation.doi10.3390/ijms23010122en
dcterms.bibliographicCitation.issue1en
dcterms.bibliographicCitation.journaltitleInternational Journal of Molecular Sciencesen
dcterms.bibliographicCitation.originalpublishernameMDPIen
dcterms.bibliographicCitation.originalpublisherplaceBaselen
dcterms.bibliographicCitation.volume23en
tub.accessrights.dnbfreeen
tub.affiliationFak. 3 Prozesswissenschaften::Inst. Biotechnologie::FG Angewandte Biochemiede
tub.affiliation.facultyFak. 3 Prozesswissenschaftende
tub.affiliation.groupFG Angewandte Biochemiede
tub.affiliation.instituteInst. Biotechnologiede
tub.publisher.universityorinstitutionTechnische Universität Berlinen

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