Effects of mesenchymal stem cell therapy on alopecia areata in cellular and hair follicle organ culture models

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-gamma). 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/beta-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/beta-catenin signalling pathway, including ss-catenin and phosphorylated GSK3b, and decreased IFN-gamma-induced expression of DKK1 in hDPCs. hHMSCs suppressed IFN-gamma-induced expression of caspase-1, caspase-3 and IFN-gamma receptor. hHMSCs induced the phosphorylation of STAT1 and STAT3 compared to controls and IFN-gamma-pretreated hDPCs. hHMSC-treated HFs enhanced several growth factor mRNAs. hHMSC pretreatment modulated IFN-gamma-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.