– CYTOKINES, GROWTH FACTORS, AND STEM CELLS: NEWEST APPROACHES TO YOUNGER LOOKING SKIN

Nils Krueger, PhD,
Neil S. Sadickb

aLake Erie College of Osteopathic Medicine, 5000
Lakewood Ranch Blvd, Bradenton, Florida, 34211
bSadick Dermatology Research Group, 911
Park Avenue, Suite 1A, New York, New York, 10075

ABSTRACT

As the population grows, there is a particular increase in the growing numbers of middle-aged and elderly people, the so-called “baby boomers.” A major need among this group is a continued increase in the desire for younger-looking skin. Areas of particular concern include: loss of elasticity, wrinkles, irregular texture, pigmentation, and dryness (1,2). This desire has led to the development of cosmeceuticals, a term first coined by Albert Kligman, MD, which, from a regulatory view in the U.S. lie in an unresolved schism between “cosmetics” and physiologically altering pharmaceuticals (APIs-active pharmaceutical agents).

This chapter takes a close look at several selected and highly promising types of cosmeceuticals including: Cytokines, Growth Factors, & Stem Cells.

TABLE OF CONTENTS

4.3.6.1 Aging

4.3.6.2 Growth Factors And Cytokines

Aging occurs via two mechanisms. These are termed intrinsic and extrinsic aging.

Intrinsic aging is inevitable and results in thinned skin, fibroblast reduction, and thinning blood vessels (3). Collagen is particularly affected, as its synthesis steadily declines with age (4). Likewise, elastin also declines with age (4,5).

Extrinsic aging primarily results from the effects of UV damage. Other causes of this type of aging include environmental factors such as smoking, pollution, and poor nutrition (3,6). This type of damage causes an up-regulation and overstimulation of epidermal and dermal cells. It leads to a deterioration of both collagen and elastin as well as other components of the dermal extracellular matrix.

Aged skin shows a decrease in extracellular matrix proteins, increased collagen degradation, and decreased fibroblasts (7). Furthermore, there is a reduction in the immune response, wound repair, and fiber synthesis (8). Free radicals, which are often caused or increased by extrinsic factors, activate matrix metalloproteinases (MMPs) leading to extracellular matrix (ECM) degradation (9). Additionally, free radicals inhibit the tissue inhibitors of these enzymes. The goal of cosmeceuticals is to mitigate some of these effects of aging.

Effective cosmeceuticals must be able to penetrate into and throughout the stratum corneum while maintaining their effectiveness. They also must have visible benefits without impacting the skin’s barrier function (10). There has been a recent surge of new cosmeceuticals and this chapter discusses the functions, limits, and benefits of some of the most promising types employed in anti-aging formulations. As stated in the abstract, these include: growth factors, cytokines, and stem cells. These newer cosmeceuticals are being utilized to enhance or restore homeostasis of the body by aiding in impacting the skin’s own natural mechanisms involved in such processes as wound repair and extracellular matrix development.

4.3.6.2 GROWTH FACTORS AND CYTOKINES

Many growth factors are involved in wound-healing, both chronic and acute. These have been introduced into the cosmeceutical world based on the hypothesis that the aging process of skin is similar to that of a chronic wound (9). Their ability to increase fibroblast and keratinocyte proliferation within the dermis, thus inducing ECM formation, supports this idea (7). Aging skin has reduced amounts of fibroblasts as well as decreased levels of growth factors. By supplementing these normal growth factors, we may allow for the natural repair of skin. This hypothesis opens up fertile ground for future studies involving anti-aging therapies for skin.

Growth factors are produced and secreted by many cell types of the skin, including fibroblasts, keratinocytes, and melanocytes. Included within these secreted growth factors are those that regulate the immune system, also known as cytokines. Cytokines are also involved in skin repair (11). Many growth factors are involved in wound repair, and thus most of the topical products contain a combination of growth factors. It is important to combine growth factors and cytokines as they work together and regulate each other throughout the healing process.

One of the safety concerns with growth factors is their size and ability to penetrate the epidermis. While growth factors and cytokines are very large hydrophilic molecules that do not easily cross the skin barrier, it has been proposed that absorption can occur via hair follicles, sweat glands, and compromised skin (12–14). Once absorbed into the epidermis, communication is able to occur between epidermal cells and cells of the dermal layers (9). Elsewhere in this book is an extensive chapter on anti-aging approaches for hair employing the living part of hair—the follicle. The chapter delves into the biological mechanisms of hair follicles and growth out of the scalp and will generate much insight into current progress in reversing graying of hair as well as reducing or minimizing hair loss.

Growth factors regulate cell growth and thus have a potential for carcinogenic transformation of cells (9). This is proposed to be largely based on the presence of vascular endothelial growth factor, VEGF. Receptors for VEGF are present on some types of melanoma cells (15). However, research on increased VEGF in melanoma has shown conflicting results to date. One study has shown an increase in melanoma cell proliferation when cells were combined with VEGF, while another failed to do so (16,17). An FDA investigation of a growth factor product determined that very large concentrations of growth factors, much higher than the levels found in topical cosmeceutical products, are required for this potential (9). Furthermore, because of the large size, minimal amounts of growth factors are entering the skin. Thus, topical application of growth factors is unlikely to have any effect on cancer growth (15).

Only gold members can continue reading. Log In or Register to continue