Abstract
Mesenchymal stem cells derived from Wharton’s jelly of the umbilical cord (UC-MSCs) have immunomodulatory properties. The aim of this study was to explore whether extracts of MSCs (MSC-Ex) could augment the low therapeutic efficacy of the whole cells in an Aspergillus fumigatus (Af)-induced atopic dermatitis (AD) model. LPS- or TNF-α/IFN-γ-stimulated keratinocytes (HaCaT cells) were treated with MSC-Ex, and the Af-induced AD model was established in BALB/c mice. In HaCaT cells, MSC-Ex treatment significantly reduced the inflammatory cytokine (IL-6, IL-1β, IL-4, IL-5 and TNF-α), iNOS and NF-κB levels, and upregulated the anti-inflammatory cytokines (IL-10 and TGF-β1). In the AD mice, the MSC-Ex group showed greatly reduced dermatitis, and lower clinical symptom scores and IgE levels. The histological dermatitis scores were also markedly lower in the MSC-Ex-treated animals compared with the MSC-treated group. Decreased levels of IFN-γ (Th1) and IL-17 (Th17), IL-4 and IL-13 (Th2) were detected in T cells and the skin tissue from the MSC-Ex treated AD mice. The therapeutic capacity of MSC-Ex was preserved after lyophilization and reconstitution. MSC-Ex treatment reproducibly suppresses dermatitis and inhibits the induction of inflammatory cytokines in the skin of AD mice. MSC-Ex is therefore a potential new treatment agent for AD.
Highlights
Atopic dermatitis (AD) is a chronic inflammatory dermatopathy that features eczematous skin lesions with severe pruritus and affects up to 20% of children and 10% of adults[1,2]
HaCaT cells were stimulated with LPS (100 μg/ml) for 28 h to investigate whether mesenchymal stem cells (MSCs)-Ex treatment generated anti-inflammatory effects in human keratinocytes
The clinical outcomes of these treatments with respect to efficiency are variable, likely due to the heterogeneity resulting from the use of bone marrow, adipose, UC blood, or UC (Wharton’s jelly)-derived MSCs, the homing efficiency of MSCs, and the different microenvironments that the engrafted cells have encountered in different studies
Summary
Atopic dermatitis (AD) is a chronic inflammatory dermatopathy that features eczematous skin lesions with severe pruritus and affects up to 20% of children and 10% of adults[1,2]. Several recent studies have indicated that the use of mesenchymal stem cells (MSCs) is a promising therapeutic approach for AD. Shin and colleagues reported that intravenously injected human adipose tissue-derived MSCs (AT-MSCs) alleviate AD by suppressing B lymphocyte proliferation and maturation via COX-2 signaling[10]. Subcutaneously injected human umbilical cord blood-derived MSCs (UCB-MSCs) have shown a dose-dependent clinical efficacy in moderate-to-severe adult AD patients in a clinical trial (phase I/IIa); about 58% of the patients in the trial exhibited a 50% reduction in the Eczema Area and Severity Index score[11]. We investigated the therapeutic effects of UC-MSC extracts (MSC-Ex) in an Aspergillus fumigatus (Af)-induced AD mouse model. The clinical therapeutic effects of MSC-Ex were found to be superior to that of MSCs
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