Simulation of ex vivo bone marrow culture: Application to chronic myeloid leukaemia growth model

The three-dimensional (3-D) architecture of the bone marrow (BM) supports the renewal, maintenance, proliferation and differentiation of haematopoietic stem cells (HSCs). Efforts have been made towards the reconstruction of an ex vivo HSC culture system, which could have several potential applications, such as the detailed understanding of normal and leukaemic haematopoiesis and expansion of haematopoietic stem cells for use in bone marrow transplantation (BMT). In this paper, a numerical model has been developed to investigate the advanced aspects of haematopoiesis, the regulatory effects of growth factor granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO) and erythropoietin (EPO) on the production of chronic myeloid leukaemia (CML) cells within a purpose-designed scaffold placed inside a perfused bioreactor. A multi-lineage cellular growth model of haematopoietic cells was incorporated in order to mimic the complexity of the diseased BM. The simulation results demonstrate that different combinations and concentrations of cytokines can alter the self-renewal, differentiation, and proliferation of CML cells and this effect is also dependent upon operation conditions and scaffold properties. The numerical model presented here enables the optimisation of scaffold design parameters and mass transfer environment necessary for developing a suitable ex vivo haematopoietic system.

► Development of a numerical model to investigate the advanced aspects of haematopoiesis.
► Regulatory effects of growth factors on the production of chronic myeloid leukaemia cells.
► Purpose-designed scaffold placed inside a perfused bioreactor.