Background: Placenta-derived mesenchymal stem cells (PD-MSCs) have unique immunomodulatory properties, and phosphatase of regenerating liver-1 (PRL-1) regulates the self-renewal ability of stem cells and promotes proliferation. Graves' ophthalmopathy (GO) is an autoimmune inflammatory disease of the orbit and is characterized by increased orbital levels of adipose tissue. Because the mechanism of inhibiting adipogenesis in orbital fibroblast (OF) with GO patients remains uncertain, the major

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... ective of the present study is to investigate the mechanisms by which PRL-1-overexpressing PD-MSCs (PD-MSCsPRL-1, PRL-1+) alleviate adipogenesis in OFs derived from GO patients.Methods: Primary OFs were isolated from orbital adipose tissue specimens from GO patients. After maturation as adipogenic differentiation, normal and GO-derived OFs were cocultured with naïve PD-MSCs and PD-MSCsPRL-1. Western blotting was conducted to evaluate the molecular mechanisms associated with adipogenesis inhibition in GO.Results: The characteristics of PD-MSCsPRL-1 were similar to those of naïve cells. OFs from GO patients underwent stimulated adipocyte differentiation and had significantly decreased lipid accumulation after coculture with PD-MSCsPRL-1 compared with naïve cell coculture. The mRNA and protein expression of adipogenic markers was decreased in PD-MSCsPRL-1. The protein expression of phosphorylated PI3K/AKT/mTOR in OFs from GO patients was downregulated by coculture with PD-MSCsPRL-1, which secreted IGFBPs. Interestingly, IGFBP2, -4, and -7 expression in PD-MSCsPRL-1, which was mediated by integrin alpha 4 (ITGA4) and integrin beta 7 (ITGB7), was higher than that in naïve cells and upregulated phosphorylated focal adhesion kinase (pFAK) downstream factors.Conclusion: In summary, PD-MSCPRL-1-secreted IGFBPs inhibit adipogenesis in OFs from GO patients by upregulating FAK and blocking IGF, providing a novel therapeutic strategy using functionally enhanced MSCs to treat degenerative diseases.