JP2024061100A - Skin stem cell proliferation promoter - Google Patents

Abstract

[Problem] To discover a new substance that has high proliferation-promoting activity against skin stem cells, and to provide it as a skin stem cell proliferation promoter. [Solution] A skin stem cell proliferation promoter or protein C receptor (PROCR) expression promoter containing pantothenyl ethyl ether as an active ingredient. [Selected Figure] None

Description

The present invention relates to a proliferation promoter for skin stem cells.

Skin is roughly divided into three layers: the epidermis, dermis, and subcutaneous tissue. Of these, the epidermis, which is the outermost layer, is mainly composed of epidermal keratinocytes. The epidermal tissue is made up of four different cell layers: the basal layer, the spinous layer, the granular layer, and the stratum corneum. Epidermal keratinocytes divide in the basal layer and move toward the upper layers, losing their ability to divide and differentiating until they reach the stratum corneum and differentiate into keratinocytes. The stratum corneum is the final differentiation product of epidermal keratinocytes, and after playing an important role in the barrier function against various external environmental factors (such as ultraviolet rays and dryness), it eventually peels off from the skin. This process of proliferation and differentiation of epidermal keratinocytes is called turnover.

Epidermal cells are periodically regenerated through this turnover, maintaining the homeostasis of the epidermis. The starting point of turnover is epidermal stem cells present in the basal layer, which are thought to play an important role in turnover. Epidermal stem cells specifically express ITGA6, ITGB1, CD271, and other marker genes for an undifferentiated state at high levels, but cells that have detached from the skin basement membrane migrate to the upper layer and mature into keratinocytes while expressing differentiation markers KRT10, FLG, and IVL. In recent years, it has been reported that the number of epidermal stem cells decreases due to aging (Non-Patent Document 1), and that INHBA/Activin-A is a factor that suppresses the proliferation of epidermal stem cells (Non-Patent Document 2). On the other hand, dermal fibroblasts can be said to be essential cells for maintaining youthful skin without wrinkles or sagging. The dermal stem cells that give rise to these dermal fibroblasts are present just below the papillary dermis, and they repeatedly proliferate and differentiate as necessary, constantly supplying new dermal fibroblasts to the dermis layer, resulting in constant regeneration of the skin. Skin aging is caused by the weakening of the regenerative ability of these skin stem cells and the lengthening of turnover. Therefore, if it is possible to promote the proliferation of epidermal cells by targeting these skin stem cells, particularly epidermal stem cells that are the starting point of turnover, it is believed that more fundamental and sustained anti-aging and regeneration of the skin can be promoted. In addition, it is believed that it is possible to efficiently obtain cultured skin by culturing epidermal stem cells outside the body, and it is expected to be very useful in transplant medicine and cosmetic applications applied to burns and wounds. However, although a method for promoting cell proliferation in epidermal keratinocytes has been reported (Patent Document 1), the method for promoting proliferation specific to epidermal stem cells and its mechanism have not been generalized, and there is currently no prospect of practical use.

On the other hand, pantothenyl ethyl ether is known to have hair growth effects such as hair regeneration, and is incorporated into hair growth compositions together with minoxidil and the like (Patent Document 2). However, the effect of pantothenyl ethyl ether in promoting the proliferation of skin stem cells has not been known until now.

JP 2019-214533 A JP 2021-134164 A

Akamatsu H. et al., Journal of Dermatology. 2016;Vol.43,No.3,pp.311-313, Age-related decrease in CD271+ cells in human skin Kawagishi-Hotta M. et al.,J Dermatol Sci. 2022; 106(3), pp.150-158, Increase in inhibin beta A/Activin-A expression in the human epidermis and the suppression of epidermal stem/progenitor cell proliferation with aging

In view of the above-mentioned circumstances, the present invention aims to discover a new substance that has high proliferation-promoting activity for skin stem cells and provide it as a skin stem cell proliferation promoter.

As a result of extensive research aimed at solving the above problems, the inventors discovered that pantothenyl ethyl ether has an excellent effect of promoting the proliferation of skin stem cells, and thus completed the present invention.

That is, the present invention includes the following inventions.
(1) A skin stem cell proliferation promoter containing pantothenyl ethyl ether as an active ingredient.
(2) A protein C receptor (PROCR) expression promoter containing pantothenyl ethyl ether as an active ingredient.
(3) The method for promoting the proliferation of skin stem cells according to (1), wherein the skin stem cells are epidermal stem cells.
(4) A composition for promoting the proliferation of skin stem cells, comprising the agent according to (1) or (2).
(5) A method for culturing skin stem cells, comprising a step of culturing skin stem cells in a medium containing pantothenyl ethyl ether.
(6) A medium for promoting the proliferation of skin stem cells, characterized by containing pantothenyl ethyl ether.

The present invention provides a skin stem cell proliferation promoter that can efficiently proliferate epidermal stem cells and dermal stem cells. Therefore, the skin stem cell proliferation promoter of the present invention is effective in treating, improving, and preventing various skin symptoms caused by dryness, ultraviolet rays, aging, etc. (skin diseases such as atopic dermatitis and dry skin, decreased barrier function and cell turnover, age spots, wrinkles, sagging, decreased firmness and elasticity, etc.), and can make a significant contribution to the fields of regenerative medicine, regenerative cosmetics, and anti-aging.

The present invention will be described in detail below.
1. Skin stem cell proliferation promoter The skin stem cell proliferation promoter and protein C receptor (PROCR) expression promoter according to the present invention (hereinafter sometimes referred to as "the agent of the present invention") contains pantothenyl ethyl ether as an active ingredient.

Pantothenyl ethyl ether used in the skin stem cell proliferation promoter of the present invention is a type of vitamin B group and is represented by the following formula (KEGG database number: D01694, molecular formula: C ₁₁ H ₂₃ NO _4, molecular weight: 233.3046).

The above pantothenyl ethyl ether is a known compound, and a commercially available product may be used, or it may be produced according to a known method.

Protein C receptor (PROCR), also known as EPCR or CD201, is known to be specifically expressed in epidermal stem cells and to be involved in the control of these stem cells. Sequence information for the PROCR gene and protein, for example in the case of humans, is registered under Genbank number: Nucleotide XM_047439830, Protein XP_047295786. In the present invention, "promoting PROCR expression" refers to promoting PROCR expression at the living body level or culture level. In addition, in the present invention, "promoting PROCR expression" refers to promoting PROCR mRNA expression and protein expression.

In the present invention, "skin stem cells" are not particularly limited as long as they are stem cells present in the epidermis, dermis, or subcutaneous adipose tissue. In the present invention, "epidermal stem cells" refer to cells capable of differentiating into epidermal keratinocytes, and "dermal stem cells" refer to cells capable of differentiating into dermal fibroblasts. Furthermore, "adipose stem cells" refer to cells capable of differentiating into adipocytes, chondrocytes, osteoblasts, and the like. The origin of the skin stem cells is not limited, and the effect can be exerted on skin stem cells of mammals such as humans, monkeys, mice, rats, guinea pigs, rabbits, cats, dogs, horses, cows, sheep, goats, and pigs.

Since pantothenyl ethyl ether has the effect of proliferating skin stem cells both at the biological level (in vivo) and at the culture level (in vitro), the agent of the present invention can be administered to mammals, including humans (monkeys, mice, rats, guinea pigs, rabbits, cats, dogs, horses, cows, sheep, goats, pigs, etc.) to proliferate skin stem cells, and can be incorporated or applied to medicines, quasi-drugs, cosmetics, etc. The agent of the present invention can also be used as a culture medium additive, research reagent, or medical reagent to promote the proliferation of skin stem cells and produce skin stem cells.

The agent of the present invention is effective in treating, improving, and preventing diseases or pathologies caused by the failure of epidermal keratinocytes or dermal fibroblasts to be formed normally due to a decrease or insufficiency in the proliferation ability of epidermal stem cells or dermal stem cells, since the active ingredient pantothenyl ethyl ether has a proliferation promoting effect on either or both of epidermal stem cells or dermal stem cells. Examples of diseases or pathologies caused by the failure of epidermal keratinocytes to be formed normally due to a decrease or insufficiency in the proliferation ability of epidermal stem cells include atopic dermatitis, psoriasis (accompanied by erythema, scales, and desquamation), delayed healing of burns and wounds, rough skin, dry skin, sensitive skin, keratinocyte hyperplasia, melasma, age spots, dullness, and open pores. Furthermore, examples of diseases or pathological conditions caused by the failure of dermal fibroblasts to be formed normally due to a reduced or insufficient proliferation ability of dermal stem cells include wrinkles, sagging skin, nasolabial folds (nasolabial folds), marionette lines, reduced firmness and elasticity, lack of moisture and luster, stiffness, dullness, solar elastosis, scleroderma, fibrosarcoma, xeroderma pigmentosum, cutaneous histiocytoma, linear atrophy of the skin (straea), wounds, burns, bedsores, scars, and birthmarks.

The amount of pantothenyl ethyl ether in the agent of the present invention is not particularly limited, but is preferably 0.00001 to 10% by weight, and more preferably 0.0001 to 1% by weight, based on the total amount of the agent. If it is less than 0.00001% by weight, the effect may not be fully exerted.

When the agent of the present invention is administered to a living body, it can be administered as is, but it can also be provided by incorporating it into various compositions such as cosmetics, quasi-drugs, and pharmaceuticals together with appropriate additives within a range that does not impair the effects of the present invention. Note that the pharmaceuticals of the present invention also include drugs for use on animals, i.e., veterinary drugs.

When the agent of the present invention is incorporated into cosmetics or quasi-drugs, the dosage form may be any of an aqueous solution system, a solubilized system, an emulsion system, a powder system, a powder dispersion system, an oil liquid system, a gel system, an ointment system, an aerosol system, a water-oil two-layer system, or a water-oil-powder three-layer system. Furthermore, the cosmetics or quasi-drugs may be produced according to methods known in the art by appropriately blending various ingredients, additives, bases, etc. that are normally used in skin topical compositions together with the agent of the present invention, selected according to their types. The form may be any of a liquid, emulsion, cream, gel, paste, spray, etc. Examples of ingredients of the skin topical composition include oils and fats (olive oil, coconut oil, evening primrose oil, jojoba oil, castor oil, hardened castor oil, etc.), waxes (lanolin, beeswax, carnauba wax, etc.), hydrocarbons (liquid paraffin, squalene, squalane, petrolatum, etc.), fatty acids (lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, etc.), higher alcohols (myristyl alcohol, cetanol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol, etc.), esters (isopropyl myristate, palmitate, etc.), and the like. isopropyl phosphate, cetyl octanoate, glycerin trioctanoate, octyldodecyl myristate, octyl stearate, stearyl stearate, etc.), organic acids (citric acid, lactic acid, α-hydroxyacetic acid, pyrrolidone carboxylic acid, etc.), sugars (maltitol, sorbitol, xylobiose, N-acetyl-D-glucosamine, etc.), proteins and protein hydrolysates, amino acids and their salts, vitamins, plant and animal extracts, various surfactants, moisturizers, UV absorbers, antioxidants, stabilizers, preservatives, disinfectants, fragrances, etc.

Types of cosmetics and quasi-drugs include, for example, lotions, milky lotions, gels, beauty serums, general creams, sunscreen creams, packs, masks, facial cleansers, cosmetic soaps, foundations, face powders, bath additives, body lotions, and body shampoos.

When the agent of the present invention is incorporated into a pharmaceutical product, it can be mixed with pharmacologically and pharmacy-acceptable additives and formulated into various preparations in a dosage form suitable for application to the affected area. As pharmacologically and pharmacy-acceptable additives, a formulation base material or carrier, excipient, diluent, binder, lubricant, coating agent, disintegrant or disintegration aid, stabilizer, preservative, antiseptic, bulking agent, dispersant, wetting agent, buffer, solubilizer or solubilization aid, isotonicity agent, pH regulator, propellant, colorant, sweetener, flavoring agent, flavoring agent, flavoring agent, etc., appropriately selected according to the dosage form and application, may be added appropriately to prepare various dosage forms that can be administered orally or parenterally, systemically or locally, by various known methods. When the pharmaceutical product of the present invention is provided in each of the above forms, it can be manufactured by a manufacturing method commonly used by those skilled in the art, for example, the manufacturing method shown in each article of the General Provisions for Preparations [2] of the Japanese Pharmacopoeia.

The pharmaceutical form of the present invention is not particularly limited, but examples thereof include oral preparations such as tablets, sugar-coated tablets, capsules, lozenges, granules, powders, liquids, pills, emulsions, syrups, suspensions, and elixirs, and parenteral preparations such as injections (e.g., subcutaneous injections, intravenous injections, intramuscular injections, and intraperitoneal injections), drips, suppositories, ointments, lotions, eye drops, sprays, transdermal absorption agents, transmucosal absorption agents, and patches. In addition, the pharmaceutical may be a dried product that is redissolved when used, and in the case of an injectable preparation, it is provided in the form of a unit-dose ampule or a multi-dose container.

For oral administration preparations, for example, excipients such as starch, glucose, sucrose, fructose, lactose, sorbitol, mannitol, crystalline cellulose, magnesium carbonate, magnesium oxide, calcium phosphate, or dextrin; disintegrants or disintegration aids such as carboxymethylcellulose, calcium carboxymethylcellulose, starch, or hydroxypropylcellulose; binders such as hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, gum arabic, or gelatin; lubricants such as magnesium stearate, calcium stearate, or talc; coating agents such as hydroxypropylmethylcellulose, white sugar, polyethylene glycol, or titanium oxide; bases such as petrolatum, liquid paraffin, polyethylene glycol, gelatin, kaolin, glycerin, purified water, or hard fat can be used, but are not limited to these.

For parenteral administration, solvents such as distilled water, physiological saline, ethanol, glycerin, propylene glycol, macrogol, alum water, vegetable oil, etc.; isotonicity agents such as glucose, sodium chloride, D-mannitol, etc.; pH adjusters such as inorganic acids, organic acids, inorganic bases, or organic bases, etc., can be used, but are not limited to these.

When the agent of the present invention is used as a medicine for treating, improving, and preventing the above-mentioned skin-related damage and diseases, the suitable form is a topical preparation, for example, an ointment, cream, gel, liquid, patch (poultice, plaster), foam, spray, or atomized agent. An ointment refers to a homogeneous semi-solid topical preparation, and includes oleaginous ointments, emulsion ointments, and water-soluble ointments. A gel refers to a topical preparation in which a water-insoluble component hydrate compound is suspended in an aqueous liquid. A liquid refers to a liquid topical preparation, and includes lotions, suspensions, emulsions, liniments, and the like.

The pharmaceutical of the present invention functions as a preventive drug to suppress the onset of the above-mentioned diseases and/or as a therapeutic drug to improve the condition to a normal state. When the agent of the present invention is used as a pharmaceutical for treating, improving, and preventing the above-mentioned diseases, it can be administered orally or parenterally in a wide range of dosages to mammals such as humans, mice, rats, rabbits, dogs, and cats.

The dosage of the pharmaceutical of the present invention can be appropriately determined depending on the type of disease, the age, sex, weight, and severity of symptoms of the subject. For example, when orally administered to an adult, the daily dosage is 0.1 to 1000 mg, preferably 1 to 500 mg, and more preferably 5 to 300 mg of the compound.

The content of the agent of the present invention in the cosmetic, quasi-drug, or pharmaceutical product of the present invention is not particularly limited, but the content of the above compound is preferably 0.001 to 30% by weight, and more preferably 0.01 to 10% by weight, based on the total weight of the formulation (composition). The above amounts are merely examples, and may be set and adjusted as appropriate taking into consideration the type and form of the composition, the general amount used, efficacy, and effects. In addition, the method of adding the active ingredient in the formulation may be added in advance or during production, and may be selected as appropriate taking into consideration workability.

2. Method for Culturing Skin Stem Cells The present invention also relates to a method for culturing skin stem cells, which comprises the step of culturing skin stem cells in a medium containing pantothenyl ethyl ether.

In the culture method of the present invention, the medium for culturing skin stem cells and the additives used at the same time are not particularly limited, and any medium and additives commonly used for the proliferation of skin stem cells (epidermal stem cells or dermal stem cells) may be used.

Specifically, the medium for culturing skin stem cells includes a basal medium containing components necessary for the survival and proliferation of stem cells (inorganic salts, carbohydrates, hormones, essential amino acids, non-essential amino acids, vitamins, and fatty acids), such as Dulbecco's Modified Eagle Medium (D-MEM), Minimum Essential Medium (MEM), RPMI 1640, Basal Medium Eagle (BME), Dulbecco's Modified Eagle Medium: Nutrient Mixture F-12 (D-MEM/F-12), and Glasgow Minimum Essential Medium (Glasgow MEM), Hank's balanced salt solution, etc. are used. In order to increase the cell growth rate, the above medium may be supplemented with growth factors such as basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF), tumor necrosis factor (TNF), vitamins, interleukins, insulin, transferrin, heparin, heparan sulfate, collagen, bovine serum albumin (BSA), fibronectin, progesterone, selenite, B27 supplement, N2 supplement, ITS supplement, etc., as well as antibiotics (penicillin, streptomycin, etc.). Each component of the medium is sterilized by an appropriate method before use.

In addition to the above, it is preferable that serum (e.g., 10% FBS) is included at a content of 1-20%. However, since serum contains different ingredients depending on the lot and its effect varies, it is preferable to check the lot before use.

A commercially available medium can be used for culturing skin stem cells. Examples of commercially available medium include Invitrogen's mesenchymal stem cell basal medium, Sanko Junyaku's mesenchymal stem cell basal medium, TOYOBO's MF medium, and Sigma's Hank's balanced salt solution.

In accordance with the above-mentioned skin stem cell proliferation promoter of the present invention or the culture method of the present invention, pantothenyl ethyl ether can be provided as a reagent kit for promoting the proliferation of skin stem cells, either alone or separately from or mixed with a culture medium. The kit can include an instruction manual, etc., as necessary. Alternatively, the above-mentioned pantothenyl ethyl ether can be mixed with a culture medium and provided as a culture medium for promoting the proliferation of skin stem cells.

The culture vessel used for culturing skin stem cells is not particularly limited as long as it is capable of culturing stem cells, and examples thereof include flasks, petri dishes, dishes, plates, chamber slides, tubes, trays, culture bags, roller bottles, etc. The culture vessel may be either non-adhesive or adhesive, and is selected appropriately depending on the purpose. Cell-adhesive culture vessels may be treated with a cell support substrate such as an extracellular matrix in order to improve adhesion to cells. Examples of cell support substrates include collagen, gelatin, poly-L-lysine, poly-D-lysine, laminin, fibronectin, etc.

The concentration of pantothenyl ethyl ether added to the medium used for culturing skin stem cells can be appropriately determined based on the content of pantothenyl ethyl ether in the skin stem cell proliferation promoter according to the present invention described above, and may be, for example, 1 to 1000 μg/mL, preferably 10 to 400 μg/mL. In addition, pantothenyl ethyl ether may be added to the medium periodically during the stem cell culture period.

The culture conditions for skin stem cells may be the same as those normally used for culturing stem cells, and no special control is required. For example, the culture temperature is not particularly limited, but is about 30 to 40°C, preferably about 36 to 37°C. The _CO2 gas concentration is, for example, about 1 to 10%, preferably about 2 to 5%. The medium is preferably replaced once every 2 to 3 days, and more preferably every day. The culture conditions can be appropriately changed within a range in which the stem cells can survive and grow.

The promotion of skin stem cell proliferation can be evaluated, for example, by whether the number of stem cells cultured in the presence of the skin stem cell proliferation promoter of the present invention is significantly increased compared to stem cells cultured in the absence of the skin stem cell proliferation promoter of the present invention. The cell number can be measured, for example, by the MTT method or WST method using a commercially available cell number measurement kit. If the measurement results show that the relative ratio of the number of skin stem cells at the start of culture to the number of stem cells after a predetermined period of culture in the presence of the skin stem cell proliferation promoter of the present invention is greater than the same relative ratio (control) when cultured in the absence of the skin stem cell proliferation promoter of the present invention, it can be determined that skin stem cell proliferation has been promoted.

The culture method of the present invention allows for efficient proliferation of skin stem cells, and the skin stem cells produced by culture can generally be cultured outside the body and then transplanted by direct injection or other means into a wound or the area where tissue is desired to be regenerated. In other words, the skin stem cells produced by the culture method of the present invention can be used as a transplant material (cell transplant agent).

The present invention will be explained in more detail below with reference to examples. However, the present invention is not limited to these examples.

Example 1: Evaluation of the effect of pantothenyl ethyl ether in promoting the proliferation of epidermal stem cells Commercially available normal human adult epidermal keratinocytes (Kurabo Industries, Ltd.) were maintained in HuMedia-KG2 medium (Kurabo Industries, Ltd.) and used in the experiment. The cells were cultured in a 10 cm dish, recovered with trypsin-EDTA, and then immunostained with an anti-CD29 antibody (BioLegend, Inc., clone: TS2/16) and an anti-CD49f antibody (BioLegend, Inc., clone: GoH3). From the stained cells, CD29bright/CD49f-positive cells were separated as epidermal stem cells and CD29dim/CD49f-negative cells were separated as non-epidermal stem cells using a FACS Melody (Becton Dickinson Japan), and then recovered.

The collected epidermal stem cells and non-epidermal stem cells were seeded at 3 x ¹⁰⁴ cells/well on a 96-well plate (FALCON). The next day, samples shown in Table 1 below (pantothenic acid: KEGG database number D07413, panthenol: KEGG database number D00193, pantothenyl ethyl ether: KEGG database number D01694) were added to the plates at concentrations of 0, 0.78, 1.56, 3.13, 6.25, 12.5, 25, and 50 μg/mL, respectively, and the plates were cultured for 48 hours.

After culturing, the medium was replaced with a color-developing reagent (CCK8: manufactured by Dojindo Co., Ltd.) and measurements were taken using an absorbance plate reader (manufactured by Molecular Devices Co., Ltd.). The relative cell count was calculated when the control without sample was set at 100%, and the cell proliferation-promoting effect was evaluated. The test results are shown in Table 2 below.

As shown in Table 2, it was confirmed that pantothenyl ethyl ether has a specific proliferation-promoting effect on epidermal stem cells. On the other hand, no proliferation-promoting effect on non-epidermal stem cells was confirmed. Pantothenic acid had no proliferation-promoting effect on either type of cell. Although panthenol had a slight proliferation-promoting effect on non-epidermal stem cells, the effect was low and it showed no effect on epidermal stem cells.

Example 2: Evaluation of the effect of pantothenyl ethyl ether in promoting PROCR expression in epidermal stem cells The epidermal stem cells and non-epidermal stem cells collected in Example 1 were seeded at 1 x ¹⁰⁵ cells/well on a 12-well plate (FALCON). The next day, pantothenic acid, panthenol, or pantothenyl ethyl ether was added to the cells at concentrations of 0, 0.78, 1.56, 3.13, 6.25, 12.5, 25, or 50 μg/mL, and the cells were cultured for 24 hours. After the culture, the cells were washed twice with PBS(-), and RNA was extracted from the cells using Trizol Reagent (Invitrogen). The extracted RNA was reverse transcribed into cDNA using a 2-STEP real-time PCR kit (Applied Biosystems), and then real-time PCR (95°C: 15 seconds, 60°C: 30 seconds, 40 cycles) was performed using the following primer set on an ABI7300 (Applied Biosystems) to confirm the expression of PROCR. Other operations were performed according to the prescribed method.

PROCR primer set:
5'-GTCTCTTCGAAGTGGCTGTG-3' (SEQ ID NO: 1)
5'-TTGTTTGGCTCCCTTTCGTG-3' (SEQ ID NO: 2)
Primer set for 18s rRNA (internal standard):
5'-CCGAGCCGCCTGGATAC-3' (SEQ ID NO: 3)
5'-CAGTTCCGAAAACCAACAAAATAGA-3' (SEQ ID NO: 4)

Expression of PROCR was evaluated by calculating the relative expression level of the PROCR gene (PROCR gene expression level/18srRNA gene expression level) as a ratio of the expression level of PROCR mRNA in cells to which no sample was added to the expression level of 18s ribosomal RNA (18srRNA), which is an internal standard, as 1, and calculating the relative expression level of the PROCR gene in cells cultured after adding the sample. The test results are shown in Table 3 below.

As shown in Table 3, it was confirmed that pantothenyl ethyl ether has the effect of promoting PROCR gene expression specifically in epidermal stem cells. On the other hand, no effect of promoting PROCR gene expression in non-epidermal stem cells was confirmed. Pantothenic acid and panthenol had no effect on either epidermal stem cells or non-epidermal stem cells.

The skin stem cell proliferation promoter of the present invention can promote the proliferation of skin stem cells in vivo or ex vivo. Therefore, the present invention can be used in the fields of cosmetics and pharmaceuticals manufacturing for treating, improving, and preventing skin diseases and pathologies caused by impaired or insufficient function of epidermal stem cells or dermal stem cells, and in the fields of transplantation materials manufacturing for regenerative medicine and regenerative beauty.

Claims (6)

A skin stem cell proliferation promoter that contains pantothenyl ethyl ether as an active ingredient. A protein C receptor (PROCR) expression promoter containing pantothenyl ethyl ether as the active ingredient. The skin stem cell proliferation promoter according to claim 1, wherein the skin stem cells are epidermal stem cells. A composition for promoting the proliferation of skin stem cells, comprising the agent according to claim 1 or 2. A method for culturing skin stem cells, comprising a step of culturing skin stem cells in a medium containing pantothenyl ethyl ether. A medium for promoting the proliferation of skin stem cells, characterized by containing pantothenyl ethyl ether.