A novel three-dimensional stromal-based model for in vitro chemotherapy sensitivity testing of leukemia cells

Abstract

The disparate response of leukemia cells to chemotherapy in vivo, compared to in vitro, is partly related to the interaction of leukemic cells and the three-dimensional bone marrow stromal microenvironment. We investigated the effects of chemotherapy agents on leukemic cell lines co-cultured with human bone marrow mesenchymal stem cells (hu-BM-MSCs) in a three-dimensional model (3D). Comparison was made to leukemic cells treated in suspension, or grown on a hu-BM-MSC monolayer (2D conditions). We demonstrated that leukemic cells cultured in 3D were more resistant to drug-induced apoptosis compared to cells cultured in 2D or in suspension. We also demonstrated significant differences in leukemic cell response to chemotherapy using different leukemic cell lines cultured in 3D. We suggest that the differential responses to chemotherapy in 3D may be related to the expression of N-cadherin in the co-culture system. This unique model provides an opportunity to study leukemic cell responses to chemotherapy in 3D.

Keywords::

• Three-dimensional
• in vitro
• leukemia
• chemotherapy sensitivity

Acknowledgements

This work was supported by an American Cancer Society Institutional Research Grant (IRG-09-062-01). We thank Marsha Danley who processed the histology specimens and Richard Hastings for his technical help with flow cytometry experiments. O.S.A. is a recipient of a research career award by the Office of Scholarly, Academic & Research Mentoring (OSARM) at his home institution, the University of Kansas Medical Center. We thank Bruce Kimler who critically reviewed the manuscript and Anna Ludlow for her help in preparing tables and bar graphs. Finally, we thank Linheng Li, PhD, for his advice regarding N-cadherin mediated leukemic cell and stroma interactions.

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