B) Methods: AD was induced in NC/Nga mice by the topical application of Dermatophagoides farinae. Naïve or activated-hUCB-MSCs were administered to mice, and clinical severity was determined. A β-hexosaminidase assay was performed to evaluate the effect of hUCB-MSCs on MC degranulation.
C) Results:The subcutaneous administration of nucleotide-binding oligomerization domain2 (NOD2)-activated hUCB-MSCs exhibited prominent protective effects against AD, and suppressed the infiltration and degranulation of mast cells (MCs). NOD2-activated MSCs reduced the MC degranulation via NOD2-COX2 signaling. In contrast to bone marrow-derived MSCs, hUCB-MSCs exerted a cell-to-cell contact-independent suppressive effect on MC degranulation through the higher production of prostaglandin E2 (PGE2). Additionally, TGF-β1 production from hUCB-MSCs in response to IL-4 via activation of STAT6 signaling contributed to the attenuation of MC degranulation by down-regulating FCεRI expression in MCs.
D) Conclusions:The subcutaneous local application of NOD2-activated hUCB-MSCs can efficiently ameliorate AD mouse model, and MSC-derived PGE2 and TGF-β1 are required for the inhibition of MC degranulation. Therefore, this study provides novel insight into the field of cell therapy for allergic disease including AD by developing highly effective MSCs and elucidating its interaction with MCs.
1. Kim HS, Shin TH, Lee BC et al. Human umbilical cord blood mesenchymal stem cells reduce colitis in mice by activating NOD2 signaling to COX2. Gastroenterology. 2013;145:1392-1403 e1391-1398.
2. Kim HS, Shin TH, Yang SR et al. Implication of NOD1 and NOD2 for the Differentiation of Multipotent Mesenchymal Stem Cells Derived from Human Umbilical Cord Blood. PloS one. 2010;5.