Mesenchymal stem cell exosomes differentially regulate gene expression of mast cells

Abstract

Emerging evidence indicates that the immunomodulatory effect of mesenchymal stem cells (MSCs) is primarily attributed to the paracrine pathway. As a key paracrine effector, MSC-derived exosomes are small vesicles that play an important role in cell-to-cell communication by carrying bioactive substances. We previously found that exosomes derived from tonsil-derived mesenchymal stem cells (T-MSCs) were able to effectively attenuate inflammatory responses in mast cells. Here we investigated how T-MSC exosomes impact mast cells in steady state, and how exposure of T-MSCs to Toll-like receptors (TLRs) ligands changes this impact. Transcriptomic analysis of HMC-1 cells, a human mast cell line, using DNA microarrays showed that T-MSC exosomes broadly regulate genes involved in the normal physiology of mast cells. TLR3 or TLR4 primed T-MSC exosomes impacted fewer genes involved in specific functions in mast cells. This distinguishable regulation also was apparent in the analysis of related gene interactions. Our results suggest that MSC exosomes maintain immune homeostasis in normal physiology and impact the inflammatory state by modulating mast cell transcription.