Phagocytosis by stroma confounds co-culture studies

Signals provided by the microenvironment can modify and circumvent pathway activities that are therapeutically targeted by drugs. Bone marrow stromal cell co-culture models are frequently used to study the influence of the bone marrow niche on ex-vivo drug response. Here we show that mesenchymal stromal cells from selected donors and NKTert, a stromal cell line which is commonly used for co-culture studies with primary leukemia cells, extensively phagocytose apoptotic cells. This could lead to misinterpretation of the results, especially if the viability readout of the target cells in such co-culture models is based on the relative proportions of dead and alive cells. Future co-culture studies which aim to investigate the impact of bone marrow stromal cells on drug response should take into account that stromal cells have the capacity to phagocytose apoptotic cells.