Topical application of ST266 reduces UV-induced skin damage

Abstract

Ultraviolet radiation (UVR) has a significant impact on human skin and is the major environmental factor for skin cancer formation. It is also believed that 80% of the signs of skin aging are attributed to UVR. UVR induces inflammatory changes in the skin via the increase in oxidative stress, DNA damage vascular permeability, and fluctuation in a myriad of cytokines. Acutely, UVR causes skin inflammation and DNA damage, which manifest as sunburn (erythema). ST266 is the secretome of proprietary amnion-derived cells that have been shown to reduce inflammation and accelerate healing of various wounds by promoting migration of keratinocytes and fibroblasts in preclinical animal studies. We hypothesized that ST266 has anti-inflammatory effects that can be used to reduce ultraviolet (UV) erythema and markers of inflammation. In this study, we examined the in vivo effects of ST266 on post UV-irradiated skin by measuring erythema, level of cyclobutane pyrimidine dimer (CPD), and expression level of xeroderma pigmentosum, complementation group A (XPA). We demonstrated that ST266 has the potential to reduce the acute effects of UV-induced skin damage when applied immediately after the initial exposure. In addition, ST266 is shown to reduce erythema, increase XPA DNA repair protein, and decrease damaged DNA.

Keywords: CPD; ST266; UV-induced DNA damage; XPA; erythema; photoaging.

Figure 1

ST266-treated sites 24 h after SSR exposure on three representative subjects. Notes: Control sites are displayed in the top left corner. Delta a values are displayed under each treated site. Delta a is the difference between the erythema of the test site and the nontest site. Black scale bar =2.54 cm. Abbreviation: SSR, simulated solar radiation.

Figure 2

Summary for delta a* 24 h post SSR exposure for all of the subjects. Notes: The mean delta a* for all 10 subject areas corresponding to no ST266 treatment 24 h post SSR is 9.99, while the mean with immediate ST266 treatment is 3.74 and the mean with delayed ST266 treatment (8–12 h post SSR) is 13.51. There was a statistically significant difference between the mean of the subject areas treated immediately with ST266 and that not treated with ST266 (p=0.00079) and between the mean of the subject areas treated with delayed ST266 and that not treated with ST266 (p=0.031). Abbreviation: SSR, simulated solar radiation.

Figure 3

Summary for delta a* 48 h post SSR exposure for all the subjects. Notes: The mean delta a* for all 10 subject areas corresponding to no ST266 treatment 48 h post SSR is 9.62, while the mean with immediate ST266 treatment is 3.56 and the mean with delayed ST266 treatment is 12.09. There was a statistically significant difference between the mean of the subject areas treated immediately with ST266 and that not treated with ST266 (p=0.0070) and a trend between the mean of the subject areas treated with delayed ST266 and that not treated with ST266 (p=0.089) 48 h post SSR. Abbreviation: SSR, simulated solar radiation.

Figure 4

Summary for delta a* 72 h post SSR exposure for all the subjects. Notes: The mean delta a* for all 10 subject areas corresponding to no ST266 treatment 72 h post SSR is 7.56, while the mean with immediate ST266 treatment is 2.97 and the mean with delayed ST266 treatment is 10.64. There was a statistically significant difference between the mean of the subject areas treated immediately with ST266 and that not treated with ST266 (p=0.010) and a marginal significance between the mean of the subject areas treated with delayed ST266 and that not treated with ST266 (p=0.065) 72 h post SSR. Abbreviation: SSR, simulated solar radiation.

Figure 5

Summary of XPA expression level measured using immunofluorescence. Notes: Six out of nine subjects showed higher XPA expression level with immediate ST266 treatment when compared with no ST266 treatment. Subjects 4 and 9 demonstrated the opposite with higher XPA expression levels after immediate ST266 treatment. Subject 1 demonstrated approximately the same XPA expression level with and without ST266 treatment. The mean fluorescence for XPA expression level without ST266 treatment is 4395 AU, while the mean XPA expression level with immediate ST266 treatment is 4824 AU. Two-tailed paired t-test was unable to demonstrate significance (p=0.55). Abbreviations: AU, arbitrary unit; UV, ultraviolet; XPA, xeroderma pigmentosum, complementation group A.

Figure 6

Summary of CPD level measured using immunofluorescence. Notes: Six out of eight subjects showed lower CPD levels with immediate ST266 treatment when compared with no ST266 treatment 24 h post SSR. Subjects 4 and 9 demonstrated the opposite with higher CPD levels after immediate ST266 treatment. The mean fluorescence intensity for CPD level without ST266 treatment is 4175 AU, while the mean CPD level with immediate ST266 treatment is 3209 AU. The difference in CPD levels between no ST266 treatment and immediate ST266 treatment is marginally significant when analyzed using two-tailed paired t-test (p=0.053). Abbreviations: AU, arbitrary unit; CPD, cyclobutane pyrimidine dimer; SSR, simulated solar radiation; UV, ultraviolet.