Please use this identifier to cite or link to this item: doi:10.22028/D291-41370
Title: Biochemical and transcriptomic evaluation of a 3D lung organoid platform for pre-clinical testing of active substances targeting senescence
Author(s): Brand, Michelle
Ritzmann, Felix
Kattler, Kathrin
Milasius, Deivydas
Yao, Yiwen
Herr, Christian
Kirsch, Susanne H.
Müller, Rolf
Yildiz, Daniela
Bals, Robert
Beisswenger, Christoph
Language: English
Title: Respiratory Research
Volume: 25
Issue: 1
Publisher/Platform: BMC
Year of Publication: 2024
Free key words: Lung diseases
Preclinical studies
Single cell sequencing
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis are incurable. Epithelial senescence, a state of dysfunctional cell cycle arrest, contributes to the progression of such diseases. Therefore, lung epithelial cells are a valuable target for therapeutic intervention. Here, we present a 3D airway lung organoid platform for the preclinical testing of active substances with regard to senescence, toxicity, and inflammation under standardized conditions in a 96 well format. Senescence was induced with doxorubicin and measured by activity of senescence associated galactosidase. Pharmaceutical compounds such as quercetin antagonized doxorubicininduced senescence without compromising organoid integrity. Using single cell sequencing, we identified a subset of cells expressing senescence markers which was decreased by quercetin. Doxorubicin induced the expression of detoxification factors specifically in goblet cells independent of quercetin. In conclusion, our platform enables for the analysis of senescence-related processes and will allow the pre-selection of a wide range of compounds (e.g. natural products) in preclinical studies, thus reducing the need for animal testing.
DOI of the first publication: 10.1186/s12931-023-02636-7
URL of the first publication:
Link to this record: urn:nbn:de:bsz:291--ds-413704
ISSN: 1465-993X
Date of registration: 8-Jan-2024
Description of the related object: Supplementary Information
Related object:
Faculty: M - Medizinische Fakultät
NT - Naturwissenschaftlich- Technische Fakultät
Department: M - Experimentelle und Klinische Pharmakologie und Toxikologie
M - Innere Medizin
NT - Biowissenschaften
NT - Pharmazie
Professorship: M - Prof. Dr. Robert Bals
M - Jun.-Prof. Dr. Daniela Yildiz
NT - Prof. Dr. Rolf Müller
NT - Prof. Dr. Jörn Walter
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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