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The skin is the largest organ of the human body, and its dysfunction is related to many diseases. There is a need to find new potential effective therapies for some skin conditions such as inflammatory diseases, wound healing, or hair restoration. Mesenchymal stromal cell (MSC)-conditioned medium (CM) provides a potential opportunity in the treatment of skin disease. Thus, the objective of this review is to evaluate the uses of MSC-CM for treating skin diseases in both animal and human models. A systematic review was conducted regarding the use of MSC-CM for treating skin conditions. One hundred one studies were analyzed. MSC-CM was evaluated in wound healing (55), hypertrophic scars (9), flap reperfusion (4), hair restoration (15), skin rejuvenation (15), and inflammatory skin diseases (3). MSC-CM was obtained from different MSC sources, mainly adipose tissue, bone marrow, and umbilical cord blood. MSC-CM was tested intravenously, intraperitoneally, subcutaneously, intradermally or intralesionally injected or topically applied. MSC-CM was used in both animals and humans. MSC-CM improved wound healing, hair restoration, skin rejuvenation, atopic dermatitis, and psoriasis in both animals and humans. MSC-CM also decreased hypertrophic scars and flap ischemia in animal models. In conclusion, MSC-CM is a promising therapy for skin conditions. Further studies are needed to corroborate safety and effectiveness and to standardize CM manufacturing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Montero-Vilchez, Sierra-Sánchez, Sanchez-Diaz, Quiñones-Vico, Sanabria-de-la-Torre, Martinez-Lopez and Arias-Santiago.)

The skin is the largest organ of the human body and its main functions include providing protection from external harmful agents, regulating body temperature, and homeostatic maintenance. Skin injuries can damage this important barrier and its functions so research focuses on approaches to accelerate wound healing and treat inflammatory skin diseases. Due to their regenerative and immunomodulatory properties, mesenchymal stromal cells (MSCs) have been reported to play a significant role in skin repair and regeneration. However, it seems that the secretome of these cells and exosomes in particular may be responsible for their functions in skin regeneration and the immunomodulation field. The present review aims to gather the available information about the role of MSC-derived exosomes for both in vitro and in vivo models of different skin conditions and to highlight the need for further research in order to overcome any limitations for clinical translation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Quiñones-Vico, Sanabria-de la Torre, Sánchez-Díaz, Sierra-Sánchez, Montero-Vílchez, Fernández-González and Arias-Santiago.)

Skin disease may be related with immunological disorders, external aggressions, or genetic conditions. Injuries or cutaneous diseases such as wounds, burns, psoriasis, and scleroderma among others are common pathologies in dermatology, and in some cases, conventional treatments are ineffective. In recent years, advanced therapies using human mesenchymal stem cells (hMSCs) from different sources has emerged as a promising strategy for the treatment of many pathologies. Due to their properties; regenerative, immunomodulatory and differentiation capacities, they could be applied for the treatment of cutaneous diseases. In this review, a total of thirteen types of hMSCs used as advanced therapy have been analyzed, considering the last 5 years (2015-2020). The most investigated types were those isolated from umbilical cord blood (hUCB-MSCs), adipose tissue (hAT-MSCs) and bone marrow (hBM-MSCs). The most studied diseases were wounds and ulcers, burns and psoriasis. At preclinical level, in vivo studies with mice and rats were the main animal models used, and a wide range of types of hMSCs were used. Clinical studies analyzed revealed that cell therapy by intravenous administration was the advanced therapy preferred except in the case of wounds and burns where tissue engineering was also reported. Although in most of the clinical trials reviewed results have not been posted yet, safety was high and only local slight adverse events (mild nausea or abdominal pain) were reported. In terms of effectiveness, it was difficult to compare the results due to the different doses administered and variables measured, but in general, percentage of wound's size reduction was higher than 80% in wounds, Psoriasis Area and Severity Index and Severity Scoring for Atopic Dermatitis were significantly reduced, for scleroderma, parameters such as Modified Rodnan skin score (MRSC) or European Scleroderma Study Group activity index reported an improvement of the disease and for hypertrophic scars, Vancouver Scar Scale (VSS) score was decreased after applying these therapies. On balance, hMSCs used for the treatment of cutaneous diseases is a promising strategy, however, the different experimental designs and endpoints stablished in each study, makes necessary more research to find the best way to treat each patient and disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sierra-Sánchez, Montero-Vilchez, Quiñones-Vico, Sanchez-Diaz and Arias-Santiago.)