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Stem cells are unspecialized cells that have two defining properties: the ability to differentiate into other cells and the ability to self-regenerate.

Stem cells have the wonderful power to develop into many different cell types in the body. When a stem cell divides, it can remain a stem cell or become another type of cell with a more specialized function like a skin cell. There are two types of stem cells, embryonic and adult.

Embryonic stem cells are exogenous in that they are harvested from outside sources, namely, fertilized human eggs. Once harvested, these stem cells are grown in cell cultures and manipulated to generate specific cell types so they can be used to treat injury or disease.


What is epidermal stem cell?

In contrast to embryonic stem cells, adult or somatic stem cells are endogenous. They are present in our bodies, from babies to adults, and serve to maintain and renovate the tissues in which they are found. Adult stem cells are found in many organs and tissues, including the skin. In actual fact, human skin is the largest depository of adult stem cells in the body. Skin stem cells dwell in the basic layer of the epidermis where they remain dormant until they are activated by tissue injury or disease.

Skin is the largest organ of the human body. It provides the first line of defense against infectious agents, and prevents dehydration and injury. Skin has a number of appendages, such as hair, sebaceous and sweat glands, that also aid in the protection of inner organs from environmental assaults. Therefore, it is of extreme importance to maintain a healthy skin, which could be achieved through replacing damaged skin cells.

The cartoon shown in Figure depicts the structure of the skin. Shown, are two layers: the dermis or inner layer that originates from mesodermal embryonic cells, and the epidermis or outer layer that are formed from ectodermal embryonic cells. These two layers are separated from each other by a basement membrane. Epidermis is a stratified tissue composed of cells called keratinocytes. The layer of keratinocytes that is closest to the basement membrane is called basal, and contains a number of constantly proliferating cells. It is these cells that migrate to the surface and form a protective layer, maintaining the outer covering of epidermis intact.

Epidermal stem cells are located in the basal layer of the epidermis. These cells give rise to transient amplifying cells that migrate to the surface and form a protective layer.

There are three main locations in the adult skin where epidermal stem cells can be found; the bulge region of the hair follicle, the interfollicular epidermis (IFE), and the sebaceous gland. Further investigation showed that the bulge region contains cells that have the ability to give rise to the stem cells in the IFE region and sebaceous gland, indicating that basal (bulge region) stem cells are more primitive than their counterparts in the other two areas.

Indeed, basal stem cells of the adult hair follicle can participate in tissue repair by responding to signals to regenerate the epidermis, hair follicles, and sebaceous glands.

A schematic diagram of an epidermopilosebaceous unit in hair-bearing skin. The unit consists of the epidermis and the hair follicle with its associated sebaceous gland. The bulge contains a population of putative keratinocyte stem cells that can give rise to (pathway 1) a population of pluripotent and rapidly dividing progenitor (transit amplifying) cells in the matrix that yields the hair shaft. Alternatively, the bulge stem cells can give rise to the stemyprogenitorcells oftheepidermis(pathway2). It is hypothesized here that the epidermal stem cell represents a form of bulge-derived, young transit amplifying cell (SCyTA1, 2….?). The long, curved arrow denotes the demonstrated capability of adult epidermal cells to form anewhair follicle in response to appropriate mesenchymal stimuli. B, bulge; E, epidermis; FP, follicular or dermal papilla; M, matrix keratinocytes; ORS, outer root sheath; S, hair shaft; SC, stem cells; SG, sebaceous gland; TA, transit amplifying cells.

In the adult, stem cells reside in the epidermal basal layer, at the base of the sebaceous gland and in a niche within the hair follicle known as the bulge. Despite intensive studies, we still know very little about how stem cells and these niches become established and maintained. Genetic marking and molecular approaches stem cells within the bulge typically cycle infrequently. In response to a skin injury, these stem cells can be mobilized to move upward, proliferate and repair epidermal wounds or replenish the sebaceous gland. In normal homeostasis, these stem cells fuel the hair cycle, where they become activated to proliferate and regenerate the hair follicle with each new anagen phase. It has been known for nearly a decade that that the transition from dormant to activated follicle stem cells involves changes in signaling by Wnts, BMPs, and other factors.

Following information is summarized to demonstrate the applicability of stem cell research to skin in animal testing by other scientists specially in medical science field.

We do NOT test on animals at any stage in ingredient nor in finished product development.

Wound repair

Epidermal stem cells play a central role in homeostasis and wound repair, and represent a cellular sources of tumor initiation and as a vehicle for gene therapy. These stem cells also have the potential for treating burn victims. Figure demonstrate hair follicle epidermal stem cells that have been used in preparing skin equivalents, forming epithelium in deep burn wounds after implantation. These experiments show hope of being able to culture autologous epithelial grafts in vitro within a short time for implantation into patients. As they show multipotency to differentiate into almost all epithelial cell types, hair follicle stem cells can be used in preparing composite skin substitutes. Scientists demonstrated that epidermal stem cells can regenerate a fully stratified epidermis by in vitro methods. Other studies found that the progenies of epidermal stem cells (transient amplifying and differentiating cells) have regenerative capacity as well(Ref.: Cell Tissue Res. 2006 Dec;326(3):725-36.).


Hair Restoration
Epidermal stem cells can also form hair follicles and have the potential to treat baldness. Researchers at the Howard Hughes Medical Institute isolated murine epidermal stem cells, and showed that a single epidermal stem cell can differentiate into skin, hair and oil glands. Elaine Fuchs and colleagues took stem cells from normal mice, and grafted them on the backs of hairless mice. They were able to show the generation of normal skin with hair ( Ref.: Cell Cycle. 2006 Feb;5(3):232-3, Ref.: PNAS 2005 Oct 11;102(41): 14653-8).

Epidermal stem cells are necessary for the maintenance of the skin. They continually self- renew and differentiate into keratinocytes in order for the skin to protect against insults. Epidermal stem cells continuously undergo self-renew to maintain the integrity of the epidermis. Ongoing research studies are in the process of identifying markers of these stem cells, although a specific marker has not been identified.

Epidermal stem cells have been demonstrated to be useful for therapeutic purposes. Due to their plasticity, it may be possible these stem cells have the ability to treat injured tissue throughout the body. Epidermal stem cells show great promise in treatment of burn patients, which is supported by results showing the ability of these cells of the hair follicle to regenerate epithelium of deep burn wounds. Also, these cells may be useful in the treatment of baldness.

Stem cell cosmetics are cosmetic products that are claimed to develop based on the stem cell technology. In a narrow meaning, they are specific products that used main ingredients originated from stem cell research.

Even stem cells are known beneficial to human, stem cell cosmetics are very slow growing. Almost main cosmetics manufacturers are afraid to involve in biological, legal and ethical problems. Stem cell cosmetics with own stem cells or derivative of stem cells will probably be involved in the problems.

Therefore, it is very important to examine and concern carefully about stem cell cosmetics before developing, manufacturing, and selling them.

Nowadays, stem cell cosmetics can divided 4 types depend on main ingredients as follows;

No cell culture problem is as universal as that of culture loss due to contamination. All cell culture laboratories and cell culture workers have experienced it. Culture contaminants may be biological or chemical, seen or unseen, destructive or seemingly benign, but in all cases there are adverse effects on cultures.

Biological contaminants can be subdivided into two groups based on the difficulty of detecting them in cultures:

• those that are usually easy to detect ? bacteria, molds and yeast;
• those that are more difficult to detect, and as a result potentially more serious culture problems, ? viruses, protozoa, insects, mycoplasmas and other cell lines.

Microbial contaminants such as bacteria or fungi, etc can achieve high densities altering the growth and characteristics of the cultures. But viral or prion contamination will not be any altering of the cultures. Due to their extremely small size, viruses or prions are the most difficult cell culture contaminants to detect in culture, requiring methods that are impractical for most research laboratories. Their small size also makes them very difficult to remove from media, sera, and other solutions of biological origin. If the use of contaminated stem cells or their extracts in cosmetics, it will be very harmful.

The study of stem cells as treatments is still at the beginning. Across the world, clinical trials on humans are rare but in the near future (5-10 years) stem cells will form a part of treatments at the bedside.

The main problem in using stem cells as therapies is the problem of removing them from their natural habit, as it is difficult to differentiate normal cells from stem cells (we do not have enough markers to identify them) and to fully understand how to maintain and control a cells ability to stay as a stem cell or to change into other cells.

A report released by an international scientific team documents that human embryonic stem cells accumulate genetic mutations as they are cultured in the lab (Maitra A et al. , Genomic alterations in cultured human embryonic stem cells, Nature Genetics Sep. 2005 ). The study compared genetic changes between cells early on in their laboratory growth and those that had been grown for longer periods of time. Like all other cells, human embryonic stem cells accumulated mutations and chromosomal changes, many of which are associated with faster growth and tumor formation . Thus embryonic stem cells pose an unusually high risk for genetic changes and tumor formation, with the risk increasing the longer the cells are grown, thus making their therapeutic use or cosmetic use even more speculative and problematic.

By contrast, adult and cord blood stem cells are usually not grown for extensive periods, so do not pose this potential of accumulating mutations. Instead, adult stem cells are generally used in patients shortly after they are harvested (or retrieved from frozen storage), and have already benefited thousands worldwide.

But Hematopoietic stem cell transplant (HSCT) recipients face a significant long-term risk for developing a second cancer, particularly if they were older at the time of transplant or received stem cells from a female donor, according to a new study. Published in the January 1, 2007 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the study reveals that within 10 years of an allogeneic HSCT, the relative risk of a second, solid cancer is almost twice that of the general population. In addition, cancer risk almost quadruples for patients who were over 40 years old at the time of transplant or for patients who received stem cells from a female donor. ( BBC News Stem cell therapy disease warning 2005/5/19 ).

If fact, cosmetic use of stem cells or extracts directly may be very harmful. Y ou introduce infection because you cannot check all the biological contaminants such as viruses, prions, etc when you take material from stem cells which are developing and where the origin is unknown. This kind of treatment can compare to the 19th century Brown-Sequard “organotherapy” whereby human diseases were treated using extracts from animal or human organs. The only reason people feel a positive effect for a month or 6 weeks after the use of stem cell cosmetics containing stem cells or stem cell extracts is because introducing foreign material into the body causes various troubles. The risks are potentially very high.

Scientists obtained scientific result that stem cell culture broth is valuable source to treat or skin care. This concept is better than that of item 1. But this case also may be dangerous.

It is generally believed that the growth of almost all types of mammalian cells in culture require the presence of added antibiotics in the culture medium. Bacterial contamination in media may seriously impair cells during culture. Maintaining sterile conditions in vitro is a great concern in most cell culture, and antibiotics are routinely added to most culture media today. Reduction or exclusion of antibiotics from media is possible but requires very strict laboratory methods which minimise the risk of contamination. Antibiotics free culture method is not general because of cost and technical problems.

Cell culture technology is used in virtually all fields of biomedical research and testing. Since the early days of cell and tissue culture, animal serum has been added to the culture media as a source of nutrients. Serum is a largely undefined, complex mixture of many and various constituents, some 200 of which have been identified so far. The effect of many of these on cultured cells remains unclear, and there is some evidence to suggest that there are cytotoxins in serum that have a detrimental effect on both primary and established cell lines. In addition, serum can harbor contaminants such as viruses, bacteria, prions and mycoplasmas.

The production of safer sources of culture soup for cosmetic use should be eliminated all animal serum together antibiotics before use. Unfortunately, this requirement is not solved by technically and economically until now.

Furthermore, there are not any scientific reports that stem cell culture broth are safe to use in cosmetics and medicine. We don’t know that the stem cells release what materials into the media during culture. We don’t also know the released materials whether safe or not although the materials are shown positive effects on the skin.

# The rules on cosmetics in the European Union are mainly aimed at ensuring that the cosmetic products sold in Member States are not harmful to health. Provisions on cosmetics prohibit outright the use of certain ingredients that have been shown to be harmful and set limits for other substances. There are also rules on instructions for use and labelling these products. Laws relating to cosmetics have been harmonised in EU Member States. Only products that comply with EU rules can be placed on the market. More than 1,000 ingredients have been entirely prohibited in the manufacturing of cosmetics. Cells, tissues or products of human origin are listed as prohibit ingredients (Ref; 1976L0768 ? EN ? 19.09.2007 ? 018.002 ? 1 ).

Stem cell cosmetics with the method are safe. In this case, the cosmetics do not actually have stem cells or stem cell derivatives including culture soap in it; the technology simply uses bio-mimickers. The stem cell or other skin cell regulators are released from stem cells during culture period. The regulators may be cytokines, peptides, proteins, minerals, chemicals or vitamins, etc. Modern biological and chemical techniques can easily define structure of the molecule. Scientists generally use various techniques including DNA chip, Proteomics, HPLC, etc. After confirm the structure, we can make a bio-mimicker by chemical synthesis or produce by genetic engineering. The method is convenient to obtain stem cell regulators but time consume.

Lots of scientific research teams in worldwide are struggling to find the new materials. Almost cosmetics manufacturers have to use the materials in the near future. „A specific molecule to awaken the body’s own reservoir of stem cells to rejuvenate the skin and make you look younger“ so the ad may state

The application of in vitro luciferase(LUC) bioluminescence systems can integrate in approach for development of new compounds which are implicated as a transcription factor regulator involved in stem cell proliferation or other skin cell proliferation. This approach includes the use of human stem cell lines transfected with luc gene under control stem cell proliferation regulators for in vitro studies.

In order to screen for compounds that act as the stem cell activator or inhibitors, we use small molecules extracted from plants. Since these small molecules have no antigens, they are not recognized as foreign by the host body and there are no allergic reactions. The use of plant origin also eliminates ethical considerations, since it causes no harm to the animal or involvement with human tissues.

In addition, these reporter lines in the evaluation of high-throughput screening hits in vitro in various models such as anti wrinkle, anti inflammation, etc are very useful potentially in stem cell research field.

here is a review proving how stem cells improve the skin.

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