Human Umbilical Cord Blood Mesenchymal Stem Cell-Derived PGE2 and TGF-β1 Alleviate Atopic Dermatitis by Reducing Mast Cell Degranulation

Abstract

Mesenchymal stem cell (MSC) is a promising tool for the therapy of immune disorders. However, their efficacy and mechanisms in treating allergic skin disorders are less verified. We sought to investigate the therapeutic efficacy of human umbilical cord blood-derived MSCs (hUCB-MSCs) against murine atopic dermatitis (AD) and to explore distinct mechanisms that regulate their efficacy. AD was induced in mice by the topical application of Dermatophagoides farinae. Na€ ıve or activated-hUCB-MSCs were administered to mice, and clinical severity was determined. The subcutaneous administration of nucleotide-binding oligomerization domain 2 (NOD2)-activated hUCBMSCs exhibited prominent protective effects against AD, and suppressed the infiltration and degranulation of mast cells (MCs). A b-hexosaminidase assay was performed to evaluate the effect of hUCB-MSCs on MC degranulation. NOD2-activated MSCs reduced the MC degranulation via NOD2-cyclooxygenase-2 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 E 2 (PGE 2 ). Additionally, transforming growth factor (TGF)-b1 production from hUCB-MSCs in response to interleukin-4 contributed to the attenuation of MC degranulation by downregulating FceRI expression in MCs. In conclusion, the subcutaneous application of NOD2-activated hUCB-MSCs can efficiently ameliorate AD, and MSC-derived PGE 2 and TGF-b1 are required for the inhibition of MC degranulation.

Umbilical cord-derived stem cells (ModulatistTM) show strong immunomodulation capacity compared to adipose tissue-derived or bone marrow-derived mesenchymal stem cells

“…This result shows that indomethacin interfered with MSCmediated suppression of lymphocytes. The results also indicate that the suppression of MSCs is associated with or mediated by PGE2, which has been previously observed for UCMSCs (Kim et al, 2015;Yu et al, 2014). However, many published publications have also suggested the role of other factors (TGFbeta, HGF, PGE 2 , NO, and IDO) in immune modulation by MSCs (Ma et al, 2014;Soleymaninejadian et al, 2012;Zhao et al, 2016).…”

Protective Effects of Ellagic Acid against UVA-induced Oxidative Stress in Human Dermal Papilla

“…MSCs can be isolated from a variety of tissues such as bone marrow, adipose tissue, skin dermis, dental pulp, hair follicle, and umbilical cord blood [1][2][3][4][5][6]. Due to their immunomodulatory and regenerative capacity, MSCs hold great potential; moreover, the advantages regarding no ethical issues unlike embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), a low risk of teratoma formation, and relatively easy obtainment have shown promising results in preclinical and clinical studies.…”

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

“…Beside the regulation of T cells and macrophages, MSCs were shown to suppress several other cells involved in the immune response including B cells [328,332,333], natural killer (NK) cells [334,335], dendritic cells [336][337][338] and mast cells [339][340][341]. Conflicting results were obtained for the interaction of MSCs and neutrophils.…”