Phagocytosis by stroma confounds coculture studies

Area of Science:

• Cell biology
• Cancer research
• Pharmacology

Background:

• Microenvironmental signals influence drug efficacy.
• Bone marrow stromal cell coculture models assess drug response in the bone marrow niche.
• Stromal cells are crucial components of the bone marrow microenvironment.

Purpose of the Study:

• To investigate the interaction between mesenchymal stromal cells and apoptotic cells in coculture models.
• To identify potential sources of error in drug response assays utilizing bone marrow stromal cell cocultures.
• To highlight the phagocytic capacity of stromal cells and its implications for experimental design.

Main Methods:

• Coculture of primary leukemia cells with mesenchymal stromal cells from selected donors.
• Coculture of primary leukemia cells with NKTert, a commonly used stromal cell line.
• Assessment of cell viability and apoptotic cell clearance in coculture systems.

Main Results:

• Mesenchymal stromal cells and NKTert demonstrate extensive phagocytosis of apoptotic cells.
• This phagocytosis can skew viability readouts, particularly those based on relative proportions of dead and alive cells.
• The engulfment of apoptotic target cells by stromal cells may lead to inaccurate drug efficacy assessments.

Conclusions:

• Stromal cell phagocytosis of apoptotic cells is a significant factor to consider in coculture models.
• Misinterpretation of drug response data is possible if this phagocytic activity is not accounted for.
• Future studies should incorporate methods to address or monitor stromal cell phagocytosis for accurate drug response evaluation.