Photoaged Skin Therapy with Adipose-Derived Stem CellsW ith great interest, we read about the article entitled "Photoaged Skin Therapy with Adipose-Derived Stem Cells," published in the June of 2020 issue of Plastic and Reconstructive Surgery by Charles-de-Sá et al. 1 In this study, 20 Brazilian candidates for face lifting were injected with in vitro-expanded, autologous, adipose-derived mesenchymal stem cells to evaluate the regeneration of dermal elastic matrix component after 3 to 4 months. The results showed a full regeneration of solar elastosis, which provided the clinical evidence and positive suggestions for prospective cellmediated therapies for skin photoaging. However, we would like to raise questions with regard to the study in some respects.First, although in the Discussion section the authors declared that no adverse effects were observed, it has been reported that cell dysfunction and risk of neoplastic transformation should be taken seriously in aging stem cells. [2][3][4] Mesenchymal stem cells derived from old donors exhibit elevated levels of reactive oxygen species, nitric oxide, lower superoxide dismutase activity, and upregulated p53 protein, so a strategy of flawless cell sorting for aged autologous therapy would be a significant issue. 5 Therefore, it is necessary to assess and reconsider the safety of adipose-derived stem cells, especially for elderly donors over 60 years old.Second, the clinical data are also important to demonstrate the therapeutic efficacy of adiposederived stem cells. Indeed, before skin biopsies were performed, application of some noninvasive detection technologies, such as dermoscopy, Raman spectroscopy, optical coherence tomography, or Visia imaging (Canfield Scientific, Inc., Parsippany, N.J.), would have been useful to analyze the changes in photoaged skin.Third, the nontreated skin specimens were considered to be the preinjection control group, while the adipose-derived, stem cell-treated skin specimens were obtained after a 3-to 4-month interval during facelifting surgery, as described in the article. However, we hold the view that biopsy specimens are far more comparable at the same time point, since the influence of the time variable should not be omitted. Furthermore, the candidates will not suffer any extra pain if the specimens of both groups are harvested during face-lifting surgery at the same time.At last, a strictly sterile laboratory environment is needed for the time-consuming and complex process, which may limit its clinical use on a large scale. To summarize, the authors' findings contribute to cellmediated therapies for sun-aged skin. We expect further studies on more stringent evaluations of safety and therapeutic efficacy.