Human induced pluripotent stem cell-derived mast cells useful for in vitro mast cell activation assay exhibiting phenotypes and morphological characteristics of human mast cells

J Toxicol Sci. 2019;44(11):789-797. doi: 10.2131/jts.44.789.

Abstract

Mast cells are key players in the inflammatory response with an important role in allergic reactions and are therefore useful for assessing the risk of anaphylaxis. However, they are difficult to isolate due to their low abundance and wide distribution. To overcome this, we generated and characterized mast cell-like cells derived from human induced pluripotent stem (hiPS) cells. These hiPS cell-derived mast cells (hiPS-MCs) were generated using recombinant human bone morphogenetic protein 4 (BMP4), vascular endothelial growth factor 165 (VEGF), stem cell factor (SCF), interleukin-4 (IL-4), interleukin-6 (IL-6), and interleukin-9 (IL-9) in a StemPro-34 medium. The hiPS-MCs exhibited the morphological characteristics of human mast cells, expressing high affinity-IgE receptor (FcεRI) and mast cell markers such as tryptase, chymase, and CD117. In addition, FcεRI stimulation with agonistic anti-IgE functionally increased the expression of activation markers CD63 and CD203c, as well as the amount of released histamine. We think the hiPS-MCs generated in this study will be useful for assessing the pharmacology and toxicity of anti-allergy medicines.

Keywords: Chymase; High affinitiy-IgE receptor; Histamine; Human induced pluripotent stem cells; Human mast cells; Tryptase.

MeSH terms

  • Cell Differentiation
  • Cell Line
  • Chymases / metabolism
  • Histamine Release
  • Humans
  • Hypersensitivity
  • Induced Pluripotent Stem Cells / cytology*
  • Interleukin-3 Receptor alpha Subunit / metabolism
  • Mast Cells / metabolism*
  • Phenotype
  • Proto-Oncogene Proteins c-kit / metabolism
  • Receptors, IgE / metabolism
  • Tryptases / metabolism

Substances

  • IL3RA protein, human
  • Interleukin-3 Receptor alpha Subunit
  • Receptors, IgE
  • KIT protein, human
  • Proto-Oncogene Proteins c-kit
  • Chymases
  • Tryptases