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Mesenchymal Stem Cells Antagonize IFN-Induced Proinflammatory Changes and Growth Inhibition Effects via Wnt/β-Catenin and JAK/STAT Pathway in Human Outer Root Sheath Cells and Hair Follicles.

ABSTRACT: Mesenchymal stem cell therapy (MSCT) has been shown to be a new therapeutic option for treating alopecia areata (AA). Outer root sheath cells (ORSCs) play key roles in maintaining the hair follicle structure and supporting the bulge area. In human ORSCs (hORSCs), the mechanism for this process has not been extensively studied. In this study, we aimed to examine the influence of human hematopoietic mesenchymal stem cells (hHMSCs) in the hORSCs in vitro model of AA and determine the mechanisms controlling efficacy. Interferon-gamma (IFN-γ) pretreatment was used to induce an in vitro model of AA in hORSCs. The effect of MSCT on the viability and migration of hORSCs was examined using co-cultures, the MTT assay, and migration assays. We investigated the expression of molecules related to the Wnt/β-catenin pathway, JAK/STAT pathway, and growth factors in hHMSC-treated hORSCs by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. hHMSCs increased hORSC viability and migration when they were co-cultured. hHMSCs reverted IFN-γ-induced expression-including NLRP3, ASC, caspase-1, CXCL-9 through 11, IL-1β, and IL-15-and upregulated several growth factors and hair stem cell markers. hHMSCs activated several molecules in the Wnt/β-catenin signaling pathway, such as in the Wnt families, β-catenin, phosphorylated GSK-3β and cyclin D1, and suppressed the expression of DKK1 induced by IFN-γ in hORSCs. hHMSCs suppressed the phosphorylation of JAK1 to 3, STAT1, and STAT3 compared to the controls and IFN-γ-pretreated hORSCs. These results demonstrate that hHMSCs increased hORSC viability and migration in the in vitro AA model. Additionally, MSCT definitely stimulated anagen survival and hair growth in an HF organ culture model. MSCT appeared to be associated with the Wnt/β-catenin and JAK/STAT pathways in hORSCs.

SUBMITTER: Lee YJ

PROVIDER: S-EPMC8123883 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundHair loss is a prevalent medical problem in both men and women. Maintaining the potential hair inductivity of dermal papilla cells (DPCs) during cell culture is the main factor in hair follicle morphogenesis and regeneration. The present study was conducted to compare the effects of different concentrations of human hair outer root sheath cell (HHORSC) and platelet lysis (PL) exosomes to maintain hair inductivity of the human dermal papilla cells (hDPCs).MethodsIn this study, hDPCs and HHORSCs were isolated from healthy hair samples. Specific markers of hDPCs (versican, α-SMA) and HHORSCs (K15) were evaluated using flow cytometric and immunocytochemical techniques. The exosomes were isolated from HHORSCs and PL with ultracentrifugation technique. Western blot was used to detect specific markers of HHORSCs and PL exosomes. Particle size and distribution of the exosomes were analyzed by NanoSight dynamic light NanoSight Dynamic Light Scattering. Different methods such as proliferation test (MTS assay), migration test (Transwell assay) were used to evaluate the effects of different concentrations of exosomes (2,550,100 µg/ml) derived from HHORSC and PL on hDPCs. Expression of specific genes in the hair follicle inductivity, including ALP, versican and α-SMA were also evaluated using real time-PCR.ResultsThe flow cytometry of the specific cytoplasmic markers of the hDPCs and HHORSCs showed expression of versican (77%), α-SMA (55.2%) and K15 (73.2%). The result of particle size and distribution of the exosomes were analyzed by NanoSight dynamic light NanoSight Dynamic Light Scattering, which revealed the majority of HHORSC and PL exosomes were 30-150 nm. For 100 µg/ml of HHORSC exosomes, the expressions of ALP, versican and α-SMA proteins respectively increased by a factor of 2.1, 1.7and 1.3 compared to those in the control group.ConclusionIn summary, we applied HHORSC exosomes as a new method to support hair inductivity of dermal papilla cells and improve the outcome for the treatment of hair loss.

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Mesenchymal Stem Cells Antagonize IFN-Induced Proinflammatory Changes and Growth Inhibition Effects via Wnt/β-Catenin and JAK/STAT Pathway in Human Outer Root Sheath Cells and Hair Follicles.

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