Activation of fibroblast metabolism in a dermal and skin equivalent model: a screening test for activity of peptides

Abstract

Skin firmness, elasticity and tone are gradually lost with age. These changes originate in the dermis and correspond to a decrease in the ability of cells, particularly the fibroblasts, to regenerate the molecules which make up the extracellular matrix. Skin ageing is also characterized by a reduction of the epidermal thickness and by a flattening of the basal membrane. The recent development of two 3-dimensional culture systems, in which the cells develop within a porous structure reproducing the extracellular matrix of the human dermis, is a way of reproducing in vivo conditions and demonstrating the biological effects of anti-ageing compounds. The dermal equivalent model used in this study is composed of a dermal matrix made of collagen-chitosan-glycosaminoglycans populated by normal human fibroblasts which synthesized their own extracellular matrix. A skin equivalent model is obtained by the cell culture of normal human keratinocytes onto a dermal equivalent elevated at the air-liquid interface. Such models were used to prove anti-ageing activity of promising compounds. Cosmetic Science has used many protein hydrolysates in order to fight skin ageing, but up to now, these natural peptides were poorly studied, and their efficacy poorly demonstrated. Eight protein hydrolysates were screened in a proliferation study in monolayered cultures giving two selected polypeptides. A soya derived peptide was used for an efficiency study in 3-dimensional models. In the dermal equivalent model, this peptide increased fibroblast proliferation by 40% and led to a stimulation of collagen formation (165%) and elastin (116%) synthesis. The effect of this soya peptide on glycosaminoglycan synthesis was also significant, with increases of 36% for chondroitin-4-sulfate and 68% for hyaluronic acid. These results were confirmed using a skin equivalent model. In this model, the soya peptide increased the thickness of the epidermis.

Synergistic action of a triple peptide complex on an essential extra‐cellular matrix protein exhibits significant anti‐aging benefits

“…A soya derived peptide has been shown in monolayer cultures as well as in skin equivalents to promote fibroblast renewal by increase their proliferative response 27 . Increased stimulation of collagen formation, elastin, and glycosaminoglycan synthesis by soya peptides has also been demonstrated 27 . The results presented in this study support previous findings that peptides can exert actions on fibroblasts which in turn influence the architectural framework of the dermis.…”

“…Plant‐derived peptides also exert biological activities. A soya derived peptide has been shown in monolayer cultures as well as in skin equivalents to promote fibroblast renewal by increase their proliferative response 27 . Increased stimulation of collagen formation, elastin, and glycosaminoglycan synthesis by soya peptides has also been demonstrated 27 .…”

Oral Supplementation of Specific Collagen Peptides Has Beneficial Effects on Human Skin Physiology: A Double-Blind, Placebo-Controlled Study

“…While chronological or intrinsic aging is characterized by a reduction of skin thickness, loss of skin elasticity, collagen fibre degeneration, xerosis and wrinkle formation [21,22,23,24,25,26,27], extrinsic or photoaging caused by sunlight exposition leads to deep-wrinkled, dyspigmented skin and the formation of small dilated blood vessels near the skin surface (telangiectasia) [28]. It can be assumed that the most prominent physiological alterations in chronological and photoaging are localized in the dermis and caused by the metabolism of dermal collagen fibres.…”

“…In experimental studies the authors examined fibroblast growth, dermal extracellular matrix synthesis, antioxidative protection and reduction of skin wrinkle formation [11,13,15,22,23,29,30,31,32,33,34]. These investigations suggested that CPs may improve skin appearance and function in skin tissue.…”

Redox Status Is Critical for Stemness in Skin Equivalents

“…So far, in vitro evaluation of skin sensitivity will be a most common application of SE models [2]. Furthermore, SE models can be used for an efficacy testing to prove antiageing activity [3] or hypopigmenting effects [4]. However, SEs will be more useful experimental models in many aspects of biology.…”