Although adipose-derived stem cells (ADSCs) have many advantageous traits compared with other postnatal stem cells, the consensus is that their differentiation potential must be improved to allow their practical utilization. During the in vitro expansion of human ADSCs (hADSCs), pre-treatment of fibroblast growth factor 2 (FGF2) not only induced an increase of approximately 44-fold in cell number at passage 7 but also augmented the differentiation potential of hADSCs. The effect of FGF2-induced cell preconditioning was evaluated by in vitro and in vivo osteogenesis after pre-treatment with various concentrations of FGF2 (0, 5, 25 ng/ml). FGF2-pre-treated hADSCs showed enhanced in vitro osteogenesis. An evaluation of in vivo osteogenic potential with an ectopic bone model showed that FGF2-preconditioned hADSCs produced an abundant osteoid/bone matrix and the effect was dependent on the concentration of FGF2 pre-treatment; bone matrix formation by control hADSCs was virtually non-existent. FGF2-pre-treated hADSCs also showed enhanced in vitro chondrogenesis, whereas no significant difference was observed in adipogenic potential. Pre-treatment of hADSCs with FGF2 induced an increase in the expression of osteogenic markers such as Cbfa1/Runx2 and alkaline phosphatase and in the expression of β-catenin. These results suggest that FGF2 plays a highly beneficial role in the preconditioning of ADSCs for musculoskeletal tissue engineering.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense pruritus and eczematous lesion. In this study, topically applied substance P (SP) significantly alleviated AD-like clinical symptoms in 2, 4, 6-trinitrochlorobenzene (TNCB)-induced dermatitis in NC/Nga mice. This effect was nullified by pretreatment of the neurokinin-1 receptor (NK-1R) antagonist CP99994. SP treatment significantly reduced the infiltration of mast cells and CD3-positive T cells as well as inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and thymic stromal lymphopoietin (TSLP), in AD-like skin lesions and decreased the levels of IgE and thymus and activation-regulated chemokine in serum. This SP-induced alleviation of allergic inflammatory responses was also confirmed as reduced activation in the axillary lymph nodes (aLN) and spleen, suggesting the systemic effect of SP on immune responses in TNCB-induced NC/Nga mice. Furthermore, SP-mediated TSLP reduction was confirmed in human keratinocyte culture under pro-inflammatory TNF-α stimulation. Taken together, these results suggest that topically administered SP may have potential as a medication for atopic dermatitis.

Topically administered SP can restore normal skin barrier function, reduce epidermal infiltration of itch-evoking nerve fibers in the AD-like skin lesions, and alleviate scratching behavior. Thus, SP may be proposed as a potential medication for chronic dermatitis and AD.