Authors
|
Bray, L. ; Binner, M. ; Körner, Y. ; Bornhäuser, M. ; Werner, C.
|
Title
|
A three-dimensional ex vivo tri-culture model mimics cell-cell interactions between acute myeloid leukemia and the vascular niche
|
Date
|
01.03.2017
|
Number
|
53069
|
Abstract
|
Ex vivo studies of human disease, such as acute myeloid leukemia, are generally limited to the analysis of two-dimensional cultures which often misinterpret the effectiveness of chemotherapeutics and other treatments. Here we show that matrix metalloproteinase-sensitive hydrogels prepared from poly(ethylene glycol) and heparin functionalized with adhesion ligands and pro-angiogenic factors can be instrumental to produce robust three-dimensional culture models, allowing for the analysis of acute myeloid leukemia development and response to treatment. We evaluated the growth of four leukemia cell lines, KG1a, MOLM13, MV4-11 and OCI-AML3, as well as samples from acute myeloid leukemia patients. Furthermore, endothelial cells and mesenchymal stromal cells were co-seeded to mimic the vascular niche for acute myeloid leukemia cells. Higher drug resistance to Daunorubicin and Cytarabine was demonstrated in three-dimensional cultures and in vascular co-cultures when compared with two-dimensional suspension cultures, opening the way for drug combination studies. Application of the C-X-C chemokine receptor type 4 (CXCR4) inhibitor, AMD3100, induced mobilization of the acute myeloid leukemia cells from the vascular networks. These findings indicate that the 3D tri-culture model provides a specialized platform for the investigation of cell-cell interactions, addressing a key challenge of current testing models. This ex vivo system allows for the personalized analysis of patient cell responses that provide new insights into acute myeloid leukemia development and therapies.
|
Publisher
|
Haematologica
|
Wikidata
|
|
Citation
|
Haematologica 102 (2017) 18 pages
|
DOI
|
https://doi.org/10.3324/haematol.2016.157883
|
Tags
|
|