title: Adipose-derived stem cells cooperate with fractional carbon dioxide laser in antagonizing photoaging: a potential role of Wnt and β-catenin signaling.
abstract: BACKGROUND
  It is well established that adipose-derived stem cells (ADSCs) produce and secrete cytokines/growth factors that antagonize UV-induced photoaging of skin. However, the exact molecular basis underlying the anti-photoaging effects exerted by ADSCs is not well understood, and whether ADSCs cooperate with fractional carbon dioxide (CO2) laser to facilitate photoaging skin healing process has not been explored. Here, we investigated the impacts of ADSCs on photoaging in a photoaging animal model, its associated mechanisms, and its functional cooperation with fractional CO2 laser in treatment of photoaging skin.
  
  
  RESULTS
  We showed that ADSCs improved dermal thickness and activated the proliferation of dermal fibroblast. We further demonstrated that the combined treatment of ADSCs and fractional CO2 laser, the latter which is often used to resurface skin and treat wrinkles, had more beneficial effects on the photoaging skin compared with each individual treatment. In our prepared HDF photoaging model, flow cytometry showed that, after adipose derived stem cells conditioned medium (ADSC-CM) co-cultured HDF photoaging model, the cell proliferation rate is higher than UVB irradiation induced HDF modeling (p < 0.05). Additionally, the expressions of β-catenin and Wnt3a, which were up-regulated after the transplantation of ADSCs alone or in combination with fractional CO2 laser treatment. And the expression of wnt3a and β-catenin has the positive correlation with photoaging related protein TGF-β2 and COLI. We also verified these protein expressions in tissue level. In addition, after injected SFRP2 into ADSC-CM co-cultured HDF photoaging model, wnt3a inhibitor, compared with un-intervened group, wnt3a, β-catenin protein level significantly decreased.
  
  
  CONCLUSIONS
  Both ADSCs and fractional CO2 laser improved photoaging skin at least partially via targeting dermal fibroblast activity which was increased in photoaging skin. The combinatorial use of ADSCs and fractional CO2 laser synergistically improved the healing process of photoaging skin. Thus, we provide a strong rationale for a combined use of ADSCs and fractional CO2 laser in treatment of photoaging skin in clinic in the future. Moreover, we provided evidence that the Wnt/β-catenin signaling pathway may contribute to the activation of dermal fibroblast by the transplantation of ADSCs in both vitro and vivo experiment.
authors.affiliation: Reconstructive and Plastic Surgery, The General Hospital of Shenyang Military Region, Shenyang, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xu
authors.affiliation: Reconstructive and Plastic Surgery, The General Hospital of Shenyang Military Region, Shenyang, P.R. China.
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Reconstructive and Plastic Surgery, The General Hospital of Shenyang Military Region, Shenyang, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Experimental Hematology, Institute of Radiation Medicine, Beijing, P.R.China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Experimental Hematology, Institute of Radiation Medicine, Beijing, P.R.China.
authors.forename: Yan-Qi
authors.initials: YQ
authors.lastname: Li
authors.affiliation: Reconstructive and Plastic Surgery, The General Hospital of Shenyang Military Region, Shenyang, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Tao
authors.affiliation: Department of Experimental Hematology, Institute of Radiation Medicine, Beijing, P.R.China.
authors.forename: Chu-Tse
authors.initials: CT
authors.lastname: Wu
authors.affiliation: Department of Experimental Hematology, Institute of Radiation Medicine, Beijing, P.R.China.
authors.forename: Ji-de
authors.initials: JD
authors.lastname: Jin
authors.affiliation: Reconstructive and Plastic Surgery, The General Hospital of Shenyang Military Region, Shenyang, P.R. China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Liu
keywords: ADSCs; CO2 fractional laser; Wnt/β-catenin signaling; photoaging