The Mechanisms and Potential Impact of Stem Cell Activation in Skin Rejuvenation: An Evidence-Based Analysis

April 2017 | Volume 16 | Issue 4 | Original Article | 378 | Copyright © April 2017

Hema Sundaram MD

Dermatology, Cosmetic and Laser Surgery, Rockville, MD and Fairfax, VA


Stem cells can propagate indefinitely in an undifferentiated state; or, with appropriate signals, differentiate into various types of mature cells. Strong interest in stem cell therapies for degenerative diseases has extended to skin aging, itself a degenerative process. This article reviews mechanisms of skin aging, and enables an evidence-based approach to topical skin rejuvenation - specifically, to formulations labeled as stem cell products.

J Drugs Dermatol. 2017;16(4):378-384.


Skin aging is characterized by exhaustion of stem cell pools, and declining migration and differentiation of cutaneous stem cells. Associated DNA damage, epigenetic alterations, and mitochondrial dysfunction are regulated by sirtuins; their transcriptional targets, including tumor suppressor proteins, p53 and p16; and cytokines, chemokines, and matrix metalloproteinases.Preservation and rejuvenation of stem cell niches reverse some phenotypic manifestations of aging.In vitro, proteins extracted from Cryptomphalus aspersa snail eggs activate stem cells from the hair follicle bulge, and assist their differentiation into fibroblasts and keratinocytes. C. aspersa extract modulates cell turnover, morphology, migration, and adhesion; improves synthesis of extracellular matrix components, and cytoskeleton organization; prevents expression of cell senescence markers, p53 overexpression, and UVB-induced premature senescence; and reduces p16 localization. These activities correlate with clinical studies of a topical formulation containing the C. aspersa snail egg signaling protein.Specific targeting and activation of cutaneous stem cells is a unique treatment strategy to address primary causes of skin aging. An evidence-based classification would define a formulation that directly impacts stem cell activation, migration, and differentiation as a stem cell product; and distinguish this from products containing stem cell-derived growth factors, cytokines, antioxidants, and peptides that primarily target existing skin cells, rather than stem cells.Overview of Skin AgingSkin aging results from a complex interaction of biological, physical, and biochemical processes that cause structural and functional damage at both molecular and cellular levels.1 Cutaneous cell senescence is characterized by DNA damage, epigenetic alterations, mitochondrial dysfunction, and stem cell exhaustion.In the skin, as in all organs, degradation of existing tissue is balanced throughout life with generation of new tissue. As the skin’s regenerative properties decline due to age-related damage, the balance of this remodeling process becomes disrupted, resulting in a net loss of tissue that is recognized as resorption. Clinically, this results in quantitative and qualitative degeneration of collagen, elastin, and other components of the skin. The underlying subcutaneous fat compartments undergo depletion, deflation, and descent; and there is loss of bone.2–8Extrinsic skin aging has been primarily attributed to the “three S’s”—sun (ultraviolet radiation), smoking, and stress. Environmental pollutants, such as sulfur dioxide and ozone, are increasingly recognized as important contributors.9 Extrinsic aging factors increase oxidative stress via reactive oxygen species overload and concomitant antioxidant depletion. The triggering of multiple biochemical pathways promotes collagen loss by inducing suppression of transforming growth factor-β receptor II; overexpression of matrix metalloproteinases (MMPs), which are collagenases; and increased inflammation through the nuclear factor-kappa B pathway. Ultraviolet radiation also causes direct damage to structural proteins of the skin.Intrinsic skin aging is related to a progressive age-related decline in antioxidant capacity, coupled with increased reactive oxygen species production from oxidative metabolism in skin cells. This contributes to oxidative stress.There is considerable variation in the rates of extrinsic and intrinsic aging, based on individual exposure to the causative factors, and hereditary predisposition.10,11