dc.identifier.uri |
http://dx.doi.org/10.15488/14372 |
|
dc.identifier.uri |
https://www.repo.uni-hannover.de/handle/123456789/14489 |
|
dc.contributor.author |
Zippel, Sabrina
|
|
dc.contributor.author |
Dilger, Nadine
|
|
dc.contributor.author |
Chatterjee, Chandralekha
|
|
dc.contributor.author |
Raic, Annamarija
|
|
dc.contributor.author |
Brenner-Weiß, Gerald
|
|
dc.contributor.author |
Schadzek, Patrik
|
|
dc.contributor.author |
Rapp, Bastian E
|
|
dc.contributor.author |
Lee-Thedieck, Cornelia
|
|
dc.date.accessioned |
2023-07-31T07:00:10Z |
|
dc.date.available |
2023-07-31T07:00:10Z |
|
dc.date.issued |
2022 |
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dc.identifier.citation |
Zippel, S.; Dilger, N.; Chatterjee, C.; Raic, A.; Brenner-Weiß, G. et al.: A parallelized, perfused 3D triculture model of leukemia for in vitro drug testing of chemotherapeutics. In: Biofabrication 14 (2022), Nr. 3, 035011. DOI: https://doi.org/10.1088/1758-5090/ac6a7e |
|
dc.description.abstract |
Leukemia patients undergo chemotherapy to combat the leukemic cells (LCs) in the bone marrow. During therapy not only the LCs, but also the blood-producing hematopoietic stem and progenitor cells (HSPCs) may be destroyed. Chemotherapeutics targeting only the LCs are urgently needed to overcome this problem and minimize life-threatening side-effects. Predictive in vitro drug testing systems allowing simultaneous comparison of various experimental settings would enhance the efficiency of drug development. Here, we present a three-dimensional (3D) human leukemic bone marrow model perfused using a magnetic, parallelized culture system to ensure media exchange. Chemotherapeutic treatment of the acute myeloid leukemia cell line KG-1a in 3D magnetic hydrogels seeded with mesenchymal stem/stromal cells (MSCs) revealed a greater resistance of KG-1a compared to 2D culture. In 3D tricultures with HSPCs, MSCs and KG-1a, imitating leukemic bone marrow, HSPC proliferation decreased while KG-1a cells remained unaffected post treatment. Non-invasive metabolic profiling enabled continuous monitoring of the system. Our results highlight the importance of using biomimetic 3D platforms with proper media exchange and co-cultures for creating in vivo-like conditions to enable in vitro drug testing. This system is a step towards drug testing in biomimetic, parallelized in vitro approaches, facilitating the discovery of new anti-leukemic drugs. |
eng |
dc.language.iso |
eng |
|
dc.publisher |
Bristol : IOP Publ. |
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dc.relation.ispartofseries |
Biofabrication 14 (2022), Nr. 3 |
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dc.rights |
CC BY 4.0 Unported |
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dc.rights.uri |
https://creativecommons.org/licenses/by/4.0 |
|
dc.subject |
Chemotherapeutics |
eng |
dc.subject |
Drug testing |
eng |
dc.subject |
Hematopoietic stem and progenitor cells |
eng |
dc.subject |
Leukemic niche |
eng |
dc.subject |
Magnetic hydrogels |
eng |
dc.subject.ddc |
570 | Biowissenschaften, Biologie
|
|
dc.title |
A parallelized, perfused 3D triculture model of leukemia for in vitro drug testing of chemotherapeutics |
eng |
dc.type |
Article |
|
dc.type |
Text |
|
dc.relation.essn |
1758-5090 |
|
dc.relation.issn |
1758-5082 |
|
dc.relation.doi |
https://doi.org/10.1088/1758-5090/ac6a7e |
|
dc.bibliographicCitation.issue |
3 |
|
dc.bibliographicCitation.volume |
14 |
|
dc.bibliographicCitation.firstPage |
035011 |
|
dc.description.version |
publishedVersion |
eng |
tib.accessRights |
frei zug�nglich |
|
dc.bibliographicCitation.articleNumber |
35011 |
|