Adipose-derived Stem Cells Promote Skin Homeostasis and Prevent its Senescence in an In vitro Skin Model

Abstract

Objectives: Skin aging is subject of many studies in esthetic surgery including several morphological changes like decrease of epidermis thickness and of cell proliferative potential. ASC, mesenchymal stem cells derived from adipose tissue, have been used in regenerative and reparative surgery as well as anti-aging solution. The aim of this study was to highlight the influence of ASCs on skin aging and healing in an in vitro skin model. Methods: Using an skin equivalent (SE) model prepared without or with ASCs in different proportion (25% or 50% of ASCs), beneficial influence of ASCs on epidermal regeneration via markers of proliferative and differentiative potential and on quality of the dermis via markers of dermal protein synthesis was analyzed. In addition, an extendedtime cultured model mimicking skin ageing was used to demonstrate ASCs influence on skin aging via markers of the quality of the epidermis and dermis as well as via a marker of senescence. Results: After 42 days of culture, SEs prepared with 25% of ASCs were thicker, presented a better proliferative potential showed by a higher number of Ki67 positive cells, and a better differentiation in epidermis. A better fibroblast synthesis in dermis was also showed. Skin ageing was studied by prolonging culture time : SEs prepared with 25% of ASCs showed remained Ki67 positive cells and a low level of senescent marker, p16, labeling, whereas SEs with fibroblasts alone were very thin, free of proliferative cells and with a high p16 expression. Conclusions: To conclude, adding ASCs in low proportion (25%) improved quality of the epidermis and dermis preventing senescence of the SE model. This confirms clinical results and supports their anti-aging effect and their potential in wound healing. In addition, this model provides a tool to elucidate the mode of action of ASCs on healing and skin aging.

Evaluation of the Secretome Profile and Functional Characteristics of Human Bone Marrow Mesenchymal Stromal Cells-Derived Conditioned Medium Suggest Potential for Skin Rejuvenation

“…CM from adipose tissue comprising of several growth factors and cytokines has also shown to demonstrate the similar effects in fibroblasts and keratinocytes [31] [32]. To further illustrate the plausible function of some of the key factors present in our CM, a schematic diagram is shown in Figure 7.…”

Organoids: An Emerging Tool To Study Aging Signature Across Human Tissues. Modeling Aging With Patient-derived Organoids

“…SE have successfully modeled some features of skin aging such as decreased ECM synthesis, cellular loss, and thinner epidermal layer [32]. SE derived from aged donors show some of these histological features of aging [33,34], and p16 has been identified as a driver of these changes, as demonstrated by the modulation of p16 levels in young-and old-derived SE [33]. Extended culture of SE also recapitulates normal skin aging, including p16 induction [35].…”

“…Extended culture of SE also recapitulates normal skin aging, including p16 induction [35]. Moreover, Metral et al [34] showed that the addition of adipose-derived stem cells delayed the expression of senescence markers in SE. SE have also been used to analyze the role of the microenvironment in age-associated changes in the skin.…”

Organoids: An Emerging Tool to Study Aging Signature across Human Tissues. Modeling Aging with Patient-Derived Organoids

“…SE have successfully modeled some features of skin aging such as decreased ECM synthesis, cellular loss, and thinner epidermal layer [35]. SE derived from aged donors show some of these histological features of aging [36,38], and p16 has been identified as a driver of these changes, as demonstrated by the modulation of p16 levels in young-and old-derived SE [36]. Extended cultures of SE also recapitulate normal skin aging, including p16 induction [37].…”

“…Extended cultures of SE also recapitulate normal skin aging, including p16 induction [37]. Moreover, Metral et al [38] showed that the addition of adipose-derived stem cells delayed the expression of senescence markers in SE. SE have also been used to analyze the role of the microenvironment in age-associated changes in the skin.…”