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

May 2016 | Volume 15 | Issue 5 | Original Article | 583 | Copyright © 2016

Gabriel Nistor MD,a Aleksandra J. Poole PhD,a Zoe Draelos MD,b Mary Lupo MD,c Thomas Tzikas MD,d Jerome H. Liu MD,e and Hans S. Keirstead PhDa

aAiVita Biomedical, Inc., Irvine, CA
bZoe Diana Draelos Dermatology Consulting Services, High Point, NC
cLupo Center for Aesthetic and General Dermatology, New Orleans, LA
dTzikasMD, Delray Beach, FL
eLiu Plastic Surgery, Los Gatos, CA

Abstract

These studies were designed to determine the effect of stem cell-derived skin lineage precursor secretions on the intrinsic and extrinsic symptoms of human skin aging.
Human stem cells cultivated in balanced conditions were differentiated into skin lineage precursors, and shown to secrete large amounts of fetuin as well as multiple growth factors beneficial for human skin development and maintenance. The cell secretions were incorporated in two simple cosmetic formulations (serum and lotion) and investigated in an IRB-approved 12-week human trial that included 25 subjects in each group. Subjects were examined at 2, 4, 8, and 12 weeks by a dermatologist to evaluate safety, trans-epidermal water loss, wrinkles, firmness, radiance, texture, softness, and overall appearance. A sub-group of subjects from each group consented for biopsies for histological analyses.
Protein analyses in the cell secretions revealed a high concentration of the multifunctional alpha 2-HS glycoprotein (fetuin) along with a multitude of protein factors involved in the development and maintenance of healthy human skin. Clinical investigation demonstrated significant amelioration of the clinical signs of intrinsic and extrinsic skin aging, findings that were confirmed by significant changes in skin morphology, filaggrin, aquaporin 3, and collagen I content.
Our data strongly support our hypothesis that cosmetic application of stem cell-derived skin lineage precursor secretions containing fetuin and growth factors beneficial for human skin development and maintenance, positively influence intrinsic and extrinsic aging.

J Drugs Dermatol. 2016;15(5):583-598.

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INTRODUCTION

Skin aging has deep social implications and has gained increasing attention as baby boomers continue to lead active lives. As a result, the importance of social “attractiveness” now affects the behavior of both genders as patients are seeking to naturally preserve a more youthful look. This has generated intense interest for the development of effective skin treatments to counteract the biologic aging of the skin.

Clinically, skin aging can be categorized into intrinsic and extrinsic aging. Intrinsic aging is a natural biologic process that leads to thinning skin, development of fine wrinkles, and deepening of facial expression lines. Extrinsic aging accentuates intrinsic aging in the form of blemished, thickened, yellowed, lax, and rough skin. These changes may begin as early as the second decade of life. 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

As the understanding and availability of stem cells has increased, there has been a 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

Advantages of Using Factors Secreted by Live Human Cells

Botanical derived growth factors differ from mammalian factors, and cannot precisely fulfill the same functions, including but not limited to cell-cell interactions, energy metabolism,

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