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J R Soc Interface. 2018 Apr;15(141). pii: 20170928. doi: 10.1098/rsif.2017.0928.

Alginate foam-based three-dimensional culture to investigate drug sensitivity in primary leukaemia cells.

Author information

1
Department of Mechanical Engineering, University College London, Torrington Place, London WC1E 7JE, UK.
2
Centre for Haematology, Department of Medicine, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
3
School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK.
4
Molecular Pathology, North West London Pathology, Hammersmith Hospital, London, W12 0HS, UK.
5
Department of Mechanical Engineering, University College London, Torrington Place, London WC1E 7JE, UK m.edirisinghe@ucl.ac.uk.

Abstract

The development of assays for evaluating the sensitivity of leukaemia cells to anti-cancer agents is becoming an important aspect of personalized medicine. Conventional cell cultures lack the three-dimensional (3D) structure of the bone marrow (BM), the extracellular matrix and stromal components which are crucial for the growth and survival of leukaemia stem cells. To accurately predict the sensitivity of the leukaemia cells in an in vitro assay a culturing system containing the essential components of BM is required. In this study, we developed a porous calcium alginate foam-based scaffold to be used for 3D culture. The new 3D culture was shown to be cell compatible as it supported the proliferation of both normal haematopoietic and leukaemia cells. Our cell differential assay for myeloid markers showed that the porous foam-based 3D culture enhanced myeloid differentiation in both leukaemia and normal haematopoietic cells compared to two-dimensional culture. The foam-based scaffold reduced the sensitivity of the leukaemia cells to the tested antileukaemia agents in K562 and HL60 leukaemia cell line model and also primary myeloid leukaemia cells. This observation supports the application of calcium alginate foams as scaffold components of the 3D cultures for investigation of sensitivity to antileukaemia agents in primary myeloid cells.

KEYWORDS:

culture, drug resistance; leukaemia; scaffold; three dimensional

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