- Laura J Bray1,*,
- Marcus Binner2,
- Yvonne Körner2,
- Malte von Bonin3,
- Martin Bornhäuser3 and
- Carsten Werner2
- 1 Queensland University of Technology, Brisbane, Australia;
- 2 Leibniz Institute of Polymer Research Dresden, Dresden, Germany;
- 3 Universitätsklinikum Carl Gustav Carus, Dresden, Germany
- ↵* Corresponding author; email:
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.
- Received October 8, 2016.
- Accepted March 27, 2017.
- Copyright © 2017, Ferrata Storti Foundation