Skin Care

skin_care

Overview

Leveraging our expertise in stem cell biology to explore new therapeutic areas, AIVITA has developed a skin care technology which aims to recreate the microenvironment responsible for the growth and maintenance of human skin. Comprised of components which support early skin development, the technology represents a novel and promising approach in the pursuit of younger, healthier looking skin.

Reference Material

Human Stem Cell-Derived Skin Progenitors Produce Alpha 2-HS Glycoprotein (Fetuin): A Revolutionary Cosmetic Ingredient

Nistor G, Poole AJ, Draelos Z, Lupo M, Tzikas T, Liu JH, Keirstead HS.

What is Skin Aging?

agedskinhand

Clinically, skin aging can be categorized into intrinsic and extrinsic aging. Intrinsic aging is a natural biological process that leads to thinning skin, the development of fine wrinkles, and the deepening of facial expression lines. Extrinsic aging accentuates intrinsic aging in the form of blemished, thickened, yellowed, lax, and rough skin.
Histologically, these aging changes are characterized by epidermal dysplasia with varying degrees of cytological atypia, loss of keratinocyte polarity, inflammatory infiltrate, decreased collagen, increased ground substance, mineral deposits, and elastosis. 1, 2, 3

Stem Cells and Cosmetics

ointmentAs the understanding and availability of stem cells has increased, so has the trend towards their use in cosmetics. Although there are many claims of efficacy resulting from the use of stem cell-based components for the treatment of intrinsic and extrinsic aging, the stem cell-based additives have rarely been satisfactorily rationalized, and a precise mechanism of action is lacking. Despite the fact that stem cells are not known for significant secretory activity, most of the observations are attributed to the presence of secreted growth factors such as FGF, EGF, TGFβ, NGF, PDGF, HGF, and others. This gap in knowledge is the basis of the current study on the mechanism of physiological action of stem cell-based additives for skin care. 4,5

The Advantage of Using Factors Secreted by Live Human Cells

  • Botanical derived growth factors differ from mammalian factors and cannot precisely fulfill the same functions, including cell-cell interactions, energy metabolism, genetic modulation, post-translational modification, and waste removal.
  • Botanical factors can cause irritation and allergies within mammalian systems due to their antigenic properties, botanical-derived products often rely on the use of toxic solvents for purification.
  • Hormones and growth factors secreted in bioreactors by bacteria or insect cells have moderate efficacy due to imperfections in folding and glycosylation, necessitating higher concentrations; Factors secreted by normal mammalian cells (bioidenticals) can fulfill physiological functions at much lower concentrations, having perfect structure and maximal compatibility.6,7,8
  • Cell sources which have been screened for infectious agents produce factors which do not present the toxic risk that botanical extracts do.
  • Normal human growth factors do not cause cell mutations, as opposed to single component growth factor systems (example FGF or EGF) which may facilitate the survival, proliferation and immune escape of already mutated cells.9
  • Many current cosmetic products based on cell lysates or extracts generated in high density bioreactors produce a foul odor as a result of degraded proteins.
  • Lipids within cell lysates may also cause irritation due to membrane fragments presenting MHC class 1 molecules and toll-like receptor signals that cause immune reaction.10,11
  • In contrast, supernatant from growing stem cell and stem cell derivate culture is composed of media containing vitamins, amino-acids, nutrients, as well as the unaltered secretions of live cells.
  • The complexity of the factors secreted by a cell population in a very early developmental stage mirrors the developmental milieu of very young organisms.

Clinical Studies

AIVITA’s skin care technology has been the subject of two independent 12-week trials that were conducted to evaluate the technology’s effect on the appearance of facial skin, assessing lines/wrinkles, firmness/elasticity, radiance, texture/smoothness and overall appearance. As the studies progressed investigators and subjects observed improvements in the appearance of wrinkles, increased firmness, softness, radiance, and finer texture.7

Figure 1: Assessment of Overall Appearance

  • Overall Appearance

Figure 2: Assessment of Individual Signs of Aging

  • Tone
  • Clarity
  • Redness
  • Fine line wrinkles
  • Roughness, softness
  • Radiance

Figure 1: Improvements in overall appearance were observed starting at week 2, with improvements in overall appearance being evaluated at 40-50% in all groups by week 12.1 Figure 2: Improvements in individual signs of aging were recorded and tracked over the 12 week period.

Figure 3:

Figure 4:

Figure 5:

Figure 3: H&E staining of control tissue from untreated area (A): thin, flattened epidermis with flaky stratum corneum. Matched contralateral tissue from treated area (B): more compact stratum corneum, better organized and more cells in stratum granulosum, homogeneous stratum basale, thicker papillary dermis and rete sub-papillare, statistically significant enhanced rete peg, P= .0387 (C). Figure 4: Filaggrin staining was much lighter in the control tissue (A) as compared to treated tissue (B). Quantification of filaggrin from biopsies of treated subjects and matched controls showed that filaggrin levels increased significantly (P< .001) in the treated area vs. matched controls (C). Figure 5: Aqaporin 3 labeling revealed increased medium and high intensity staining of the treated tissue (B), compared to control (A). Quantification
reflects a statistical trend of increased labeling in treated tissue (C).

Figure 6:

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Figure 7:

Fig7

Figure 6: Subject photo. (A) Baseline, (B) 12 weeks after application of test material. Figure 7: Subject photo. (A) Baseline, (B) 12 weeks after application of test material.

References

  1. Farage MA, Miller KW, Elsner P, Maibach HI. Intrinsic and extrinsic factors in skin ageing: a review. Int J Cosmet Sci. 2008 Apr; 30(2):87-95.
  2. Gilchrest BA: Overview of skin aging. J Cut Aging & Cos Derm. 1998; 1(1):1-2.
  3. Klingman AM, Klingman LH: Photoaging. In: Fitzpatick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF (eds.): Dermatology in General Medicine, Vol. II. New York, NY: McGraw-Hill. 1993; 2972-2970.
  4. Kim JH, Jung M, Kim HS, et al. Adipose-derived stem cells as a new thera­peutic modality for ageing skin. Exp Dermatol. 2011; 20(5):383-387.
  5. Lin CS, Xin ZC, Deng CH, et al. Defining adipose tissue-derived stem cells in tissue and in culture. Histol Histopathol. 2010; 25(6):807-815.
  6. Yun UW, Yan Z, Amir R, et al. Plant natural products: history, limitations and the potential of cambial meristematic cells. Biotechnol Genet Eng Rev. 2012; 28:47-59.
  7. Simpson EL, Law SV, Storrs FJ. Prevalence of botanical extract allergy in patients with contact dermatitis. Dermatitis. 2004 Jun; 15(2):67-72.
  8. Antignac E, Nohynek GJ, Re T, Clouzeau J, Toutain H. Safety of botanical ingredients in personal care products/cosmetics. Food Chem Toxicol. 2011 Feb; 49(2):324-41.
  9. Garber AJ. Biosimilar products are not bioidentical. J Diabetes. 2015 Mar; 7(2):153-4.