Gingiva-Derived Mesenchymal Stem Cells Attenuate Imiquimod- (IMQ-) Induced Murine Psoriasis-Like Skin Inflammation

Abstract

Human gingiva-derived mesenchymal stem cells (GMSCs) are isolated from the gingival propria with promising regenerative, immunomodulatory, and anti-inflammatory properties. Recently, several studies, including ours, have found that GMSCs have the therapeutic potentials of nerve regeneration and skin disorders in various types such as the cell itself, cell-free conditioned medium, or extracellular vesicles (EVs). However, the mechanobiological behavior of GMSCs is closely related to the culture conditions. Therefore, the purpose of this study was to evaluate the function of human GMSCs on imiquimod- (IMQ-) induced murine psoriasis-like skin inflammation in two-dimensional (2D) and three-dimensional (3D) culture conditions. Here, we isolated and characterized GMSCs in 2D and 3D culture conditions and found that GMSCs in 2D and 3D infusion can significantly ameliorate the IMQ-induced murine psoriasis-like skin inflammation, reduce the levels of Th1- and Th17-related cytokines IFN-γ, TNF-α, IL-6, IL-17A, IL-17F, IL-21, and IL-22, and upregulate the percentage of spleen CD25+CD3+ T cells while downregulate the percentage of spleen IL-17+CD3+ T cells. In summary, our novel findings reveal that GMSCs in 2D and 3D infusion may possess therapeutic effects in the treatment of psoriasis.

Therapeutic effects of mesenchymal stem cells and their derivatives in common skin inflammatory diseases: Atopic dermatitis and psoriasis

“…Moreover, Ye et al. found that intravenous administration of human gingiva-derived MSCs in mice (2 × 10 6 cells) can reduce the levels of pro-inflammatory cytokines including IFN-γ, TNF-α, IL-6, IL-17A, and IL-21 secreted by Th1 and Th17 cells and promote the increasing number of Treg cells in mouse psoriasis-like models ( 21 ). However, studies on the application and comparison of different types of MSCs in skin inflammatory diseases are still lacking.…”

“…Xiong et al found that subcutaneous or intravenous administration of MSCs isolated from human exfoliated deciduous teeth (SHEDs), a special type of MSCs with superior capability of immunoregulation, in mice (2 × 10 6 cells) can effectively improve the disruption of skin barrier function and enlarged spleens, decrease the levels of IgE and TLSP, and inhibit the activation of Th1, Th2, and Th17 cells in skin lesion (57). Moreover, Ye et al found that intravenous administration of human gingiva-derived MSCs in mice (2 × 10 6 cells) can reduce the levels of pro-inflammatory cytokines including IFN-g, TNF-a, IL-6, IL-17A, and IL-21 secreted by Th1 and Th17 cells and promote the increasing number of Treg cells in mouse psoriasis-like models (21). However, studies on the application and comparison of different types of MSCs in skin inflammatory diseases are still lacking.…”

“…Mesenchymal stem/stromal cell (MSC) derivatives have been widely used in clinical treatments in virtue of their abilities of regeneration, differentiation, and immunoregulation ( 15 , 16 ). The resources of MSCs can be harvested from various tissues including umbilical cord (UC-MSCs) ( 17 ) or its blood (UCB-MSCs) ( 18 ), bone marrow (BM-MSCs) ( 19 ) or adipose tissue (AD-MSCs) ( 20 ), and gingiva (GMSCs) ( 21 ), which may have different therapeutic effects on skin inflammatory diseases. In addition to those resources, there are also some important issues to be considered in stem cell-based therapy, such as the number of cells transplanted, preconditioning of the cell preparation, relevant targets of the therapy, and route and frequency of administration ( 22 – 24 ).…”