Mesenchymal stem cell therapy (MSCT) has been suggested as a new therapeutic strategy for immunological disorders. There have been only a few attempts to treat alopecia areata (AA) with MSCT. MSCT efficacy and mechanism of action in treating AA are not known. We sought to investigate the effect of human hematopoietic mesenchymal stem cells (hHMSCs) on an in vitro model of AA and to explore relevant mechanisms that regulate efficacy. An AA‐like environment was induced by pretreatment of human dermal papilla cells (hDPCs) with interferon gamma (IFN‐γ). hHMSCs were administered to the hDPCs, and cell viability was determined. Similar studies were also conducted with human hair follicles (HFs) in culture. The change in expression of the Wnt/β‐catenin pathway and JAK/STAT pathway‐related molecules and growth factors in hHMSC‐treated hDPCs was also examined by reverse transcription‐PCR, Western blot assay and growth factor array. Immune privilege–related molecules were examined by immunohistochemistry in HF culture models. hHMSCs enhanced the cell viability of the hDPCs. hHMSCs activated several molecules in the Wnt/β‐catenin signalling pathway, including ß‐catenin and phosphorylated GSK3b, and decreased IFN‐γ‐induced expression of DKK1 in hDPCs. hHMSCs suppressed IFN‐γ‐induced expression of caspase‐1, caspase‐3 and IFN‐γ receptor. hHMSCs induced the phosphorylation of STAT1 and STAT3 compared to controls and IFN‐γ–pretreated hDPCs. hHMSC‐treated HFs enhanced several growth factor mRNAs. hHMSC pretreatment modulated IFN‐γ–induced expression of molecules related to HF immune privilege on HFs in organ culture. These data suggest MSCT may be a new potential therapeutic option in treating AA.

Malassezia species are associated with several common dermatologic conditions including pityriasis versicolor, seborrhoeic dermatitis, folliculitis, and atopic dermatitis and dandruff. However, its causal role remains to be established. We intended to explore the role of inflammasome activation in human keratinocytes in response to three different Malassezia species. We compared the different activation patterns of inflammasomes and the expression of pro‐inflammatory cytokines and antimicrobial peptides by three different Malassezia species—M. restricta, M. globosa and M. sympodialis—in human keratinocytes. We found that different Malassezia species, especially M. restricta and M. globosa could induce nucleotide‐binding oligomerisation domain, leucine‐rich repeat and pyrin‐domain‐containing protein (NLRP)3–apoptosis‐associated speck‐like protein containing CARD (ASC) inflammasome activation and subsequent interleukin (IL)‐1β secretion in human keratinocytes. Malassezia species variably induced thymic stromal lymphopoietin, β‐defensin 2, and LL‐37. IL‐8 mRNA and IL‐22 protein significantly increased in the M. sympodialis‐treated group, and Chemokine C–C motif ligand (CCL)17 and CCL22 mRNA were increased in response to M. globosa‐ and M. restricta‐ treated keratinocytes, respectively. Our data show that various species of Malassezia promote variable inflammatory responses in keratinocytes by activating NLRP3 inflammasomes, pro‐inflammatory cytokines and chemokines, and antimicrobial peptides.

Background: The ceramide is known to play an important role in the formation of intracellular lipids, and play a crucial role as a barrier for skin and hair cuticle. Recent study has revealed that ceramide has potential effect on hair growth in a mouse model. However, the role of ceramide in human dermal papilla cells (hDPCs) known to play an important role in hair growth is not well understood yet. Objective: The goal of this study was to investigate the effect of synthetic ceramides (oleyl and stearyl ceramides) on hair growth using hDPCs. Methods: hDPCs were treated with synthesized ceramides. hDPCs viability was evaluated by MTT assay. The expression of hair growth related factors were investigated by western blot, real-time polymerase chain reaction and growth factor array. The expression of β-catenin was confirmed by immunofluorescence. Results: Treatment with ceramides increased the expression of proteins affecting cell proliferation such as Bcl-2, BAX, phosphorylated-ERK and Cyclin D1. Also, ceramides treatment were increased the expression of several growth factors, including epidermal growth factor family, and promote the expression of Wnt/ β-catenin and BMP2/4 signaling. Conclusion: Our data suggest that synthetic ceramides stimulates hair growth by induction proliferation of hDPCs via modulation of Wnt/β-catenin and BMP2/4 signaling. (Ann Dermatol 31(2) 164∼

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