Photoaging is one major exogenous factor of skin aging. Ultraviolet A (UVA) and ultraviolet B (UVB) irradiation induces reactive oxidative species (ROS) generation, mitogen-activated protein kinase (MAPK) signaling pathway activation, and transforming growth factor β/Smad (TGF-β/Smad) signaling pathway inhibition [[1], [2], [3], [4]]. Meanwhile, ultraviolet irradiation enhances nuclear factor-kappa B (NF-κB) and matrix metalloproteinases (MMPs) expression, causes DNA damage and cell apoptosis [[1], [2], [3], [4]]. Morphologically skin photoaging is characterized with epidermis thinning, basement membrane destruction, dermal collagens degradation, elastic tissue degeneration, dyspigmentation, and telangiectasis. The incidence of precancerous lesions and malignancies increases significantly as well [1,2]. Retinoids, anti-oxidants, herbal medicines, lasers, intense pulsed light, radiofrequencies, photodynamic therapy, and chemical peels are currently regular anti-photoaging approaches [[5], [6], [7], [8], [9], [10]]. Nevertheless, the issues of limited efficacy or duration, high risks of adverse events, and failure to enhance dermal fibroblasts amount and function, remained unresolved.

As a research and translational medicine hotspot in recent years, stem cells not only fulfill biological functions by differentiating into target cells, the secreted cytokines, chemokines, growth factors, proteases, and microRNAs are also important mechanisms [11]. Conditioned medium (CM) is rich in production and may be utilized as a cell-free alternative to stem cell therapy. Compared with traditional stem cell applications, conditioned medium has a series of advantages including high yield, flexible dose and administration, low risk of immune rejection, low probability of allergy, and convenience of transportation [12,13].

The composition of conditioned medium has been elucidated with proteomic techniques. Conditioned medium contains vascular endothelial derived growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin like growth factor I (IGFI), epidermal growth factor I (EGF-I), insulin-like growth factor II (IGF-II), basic fibroblast growth factor (bFGF), granulocyte colony stimulating factor (GCSF), monocyte chemotactic protein 1 (MCP1), etc. [14,15]. The cytokine cocktail could be deemed as theoretical basis for the potential clinical application.

Mesenchymal stem cell conditioned medium (MSC-CM) has been studied extensively and proved to be multifunctional in basic researches, including scar prevention [16], anti-UVB photodamage [17], anti-photoaging [18], anti-proliferation [19], inflammation regulation [20], and wound healing facilitation [21]. The clinical applications, including anti-photoaging [22], skin rejuvenation [23], scar treatment [24], and hair growth promotion [25] have been reported as well.

Skin-derived precursors (SKPs) isolated from the dermis are poorly immunogenic [26], and superior to the other stem cells of skin origin in differentiation potential and neural function recovery [27]. However, skin-derived precursors decrease sharply with aging [28], which limited the relevant studies. The research and application of skin-derived precursors conditioned medium (SKP-CM) have never been reported. Noteworthily, the culture routine for floating skin-derived precursors is distinct from adherent stem cells (for instance, mesenchymal stem cells, MSCs). With the addition of fresh growth factors every 3 days, the serum-free skin-derived precursor culture medium has been retained for the whole culture cycle of 10–12 days. Presumably SKP-CM may contain multiple and high-concentration cytokines due to the unique culture method, which implies a variety of biological functions.

Our previous study demonstrated that mouse skin-derived precursors (mSKPs) alleviated UVB irradiation damage via early activation of TGF-β/smad signaling pathway by thrombospondin1 (TSP1) [28]. In the present study, we aimed to explore the impact of mSKPs conditioned medium (mSKP-CM) on photoaging both in vitro and in vivo, and to elucidate the possible underlying mechanisms.