Phagocytosis by stroma confounds coculture studies
Sophie A. Herbst,
Marta Stolarczyk,
Tina Becirovic,
Felix Czernilofsky,
Yi Liu,
Carolin Kolb,
Mareike Knoll,
Marco Herling,
Carsten Müller-Tidow,
Sascha Dietrich
Affiliations
Sophie A. Herbst
Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; European Molecular Biology Laboratory (EMBL), Heidelberg, Germany; Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany; Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Biosciences, University of Heidelberg, Heidelberg, Germany
Marta Stolarczyk
Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany
Tina Becirovic
Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
Felix Czernilofsky
Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; European Molecular Biology Laboratory (EMBL), Heidelberg, Germany; Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany
Yi Liu
Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
Carolin Kolb
Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
Mareike Knoll
Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
Marco Herling
Department I of Internal Medicine, Center for Integrated Oncology Aachen-Bonn-Cologne-Duesseldorf (CIO ABCD), University of Cologne, Cologne, Germany; Clinic of Hematology, Cellular Therapy and Hemostaseology, University of Leipzig, Leipzig, Germany
Carsten Müller-Tidow
Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; European Molecular Biology Laboratory (EMBL), Heidelberg, Germany; Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany
Sascha Dietrich
Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; European Molecular Biology Laboratory (EMBL), Heidelberg, Germany; Molecular Medicine Partnership Unit (MMPU), Heidelberg, Germany; Department of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany; Corresponding author
Summary: Signals provided by the microenvironment can modify and circumvent pathway activities that are therapeutically targeted by drugs. Bone marrow stromal cell coculture 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 coculture studies with primary leukemia cells, extensively phagocytose apoptotic cells. This could lead to misinterpretation of results, especially if viability readouts of the target cells (e.g. leukemic cells) in such coculture models are based on the relative proportions of dead and alive cells. Future coculture 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.
