Mportance in clinical and cosmetic fields, how to efficiently prevent photoaging and/or to treat photoaged skin has been a focus of research. One primary mechanism by which UV causes photoaging is the suppression of synthesis of type I procollagen (COLI) [2,3], a major structural protein in the skin connective tissue which is mainly produced by the fibroblasts located within dermis. Therefore, understanding how the generation of COLI is controlled, is one of the keys to develop effective therapeutic treatment which can be used to restore the expression of COLI in the photodamaged skin. The TGF-/Smad pathway is the major regulator of synthesis of several components of the extracellular matrix, including type I and type III collagen by skin fibroblasts. It is TGF- stimulates fibroblast proliferation in the dermis to enhance collagen synthesis [4-7]. Dermal thickness was reduced in TGF2 deficient mice, but not in TGF-1 and TGF-3 deficient mice [8]. Previous studies suggested that a number of signaling pathways govern the production of COLI [9-11], one of which is the highly conserved Wnt/-catenin pathway. Wnt molecules affect cell membrane through paracrine and autocrine functions. So far, among known Wnt protein family members, Wnt1 [12,13], Wnt3a [14] and Wnt8 [15] are able to activate classical Wnt–catenin-LEF/TCF pathway, and Wnt3a upregulates TGF- in a -catenin dependent manner through Smad2, and inducts the differentiation of myofibroblast [16]. Wnt/-catenin signaling integrates signals from numerous signaling pathways including TGF- and FGF to mediate a variety of cellular activities including cell proliferation and differentiation, suggesting that Wnt/-catenin plays important roles in mediating COLI production and skin damage through TGF-. Adipose-derived stem cells (ADSCs) exhibit the ability to self-renew, proliferate and differentiate into multiple lineage-specific cells in response to different stimuli, therefore, is an ideal source for tissue engineering and regenerative medicine. Indeed, ADSCs and its conditioned medium (CM) that contains a variety of cytokines and growth factors [17], facilitated the wound healing processes by stimulating collagen synthesis in both vitro and vivo, such as in micropig and human patient [18,19]. As one of five major growth factor families have been studied with regard to the wound-healing process, ADSCs secreted growth factor, TGF-, it appears to be the most potent stimulator to collagen remodeling by fibroblasts [20,21]. However, the molecular basis underpinning the reduced UV exposure-induced skin damage by ADSCs application is PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28461585 not well understood.Another effective way for the treatment of pathological conditions of skin such as photoaging skin is the application of fractional CO2 laser, which has been well documented [22-24]. A combined use of fractional CO2 laser and other skin damage treatments such as radiofrequency waves was also proposed in order to achieve the best efficacy of treatment [25], however, whether the application of ADSCs and the use of fractional CO2 laser can be combined in clinical use had not been realized until recently. Zhou BR et al. reported that sequential use of fractional CO2 laser followed by ADSCs-CM enhanced wound healing [26]. However, the molecular mechanisms underlying the AKB-6548 site improved benefits achieved by the combined use of these different treatments remain enigmatic. In the present study, we investigated the impacts of ADSCs alone or in combination with fr.
