Generation of Macrophages from Cynomolgus-Monkey Bone Marrow as a Model to Evaluate Effects of Drugs on Innate Immunity

Curr Protoc Toxicol. 2019 Jun;80(1):e74. doi: 10.1002/cptx.74. Epub 2019 Apr 14.

Abstract

Macrophages are innate immune cells that play important roles in various physiological and pathological processes. Evaluation of pro-inflammatory effects of drugs on macrophages has become commonplace in preclinical drug development prior to human clinical trials. Despite their body-wide distribution, tissue macrophages are often difficult to collect from large animals and humans in a noninvasive manner. Therefore, in vitro-differentiated macrophages are important tools to facilitate cross-species analysis of macrophage function. Although cynomolgus monkeys are an essential non-rodent species for preclinical research, in vitro differentiation of cynomolgus-monkey macrophages has been poorly characterized. In the present unit, we describe a protocol to differentiate cynomolgus-monkey macrophages from isolated bone marrow mononuclear cells (BMMCs). In contrast to monocytes, cynomolgus-monkey BMMCs show robust expansion in the presence of macrophage colony-stimulating factor in vitro, which allows expansion of many cells from a single animal donor. Macrophages differentiated from BMMCs retain many of the macrophage phenotypes and functions, including phagocytosis and cytokine release, and therefore can be used as a surrogate to assess effects of drugs on cynomolgus-monkey macrophages. © 2019 by John Wiley & Sons, Inc.

Keywords: cynomolgus bone marrow-derived macrophages; cytokine release; flow cytometry; phagocytosis.

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects*
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Drug Evaluation
  • Immunity, Innate / drug effects*
  • Immunophenotyping
  • Macaca fascicularis
  • Macrophages / drug effects*
  • Macrophages / immunology