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Human Epidermal Keratinocyte Stem Cells and Epidermal Regeneration

Tissue-specific stem cells are essential cells that are generated during an individual’s growth and then maintain the health of tissues throughout their lifetime. These cells are found in tissues like the skin and intestines. These stem cells create new cells to replace old ones, ensuring the normal functioning of tissues.

On the other hand, the decline in biological functions with aging is attributed to various causes, and one of them is the reduced function and quantity of tissue-specific stem cells. As a person ages, the activity of these stem cells slows down or their numbers decrease. As a result, the production of new cells diminishes, leading to difficulties in tissue repair and regeneration.

The passage of time during aging and the changes in stem cells play a significant role in how these processes occur and how they impact the aging of tissues, organs, and individuals. This is a crucial theme in aging research.

In the outermost layer of the skin, there are cells known as epidermal keratinocytes. These cells start dividing in a region called the basal layer. Gradually, some of these dividing cells move through the spinous layer and granular layer, maturing in the process.

Ultimately, these cells lose their nucleus and form a layer called the stratum corneum, which contributes to the skin’s protective barrier. The process through which undifferentiated cells born in the basal layer transform into corneocytes, which constitute the barrier, is called keratinization. Keratinocytes in the stratum corneum are renewed approximately every 1 to 1.5 months.

Constantly, new epidermal keratinocytes are generated in the basal layer. Supporting this process are the “epidermal keratinocyte stem cells.” These stem cells divide into keratinocyte stem cells with the same capabilities and transient amplifying cells (TA cells) that have a limited proliferative ability. TA cells undergo several divisions, giving rise to numerous keratinocytes. Through this progression, the epidermis maintains its health.

A portion of epidermal keratinocytes isolated from human skin demonstrates the ability to form colonies in a cultured environment. Among them, colonies formed by keratinocyte clones, consisting of cells with consistently high proliferative abilities, are known as “holoclones.” Holoclones can divide more than 180 times under optimal culture conditions and theoretically generate enough keratinocytes to cover the entire body surface.

Furthermore, these keratinocyte stem cells can create cell sheets with epidermal-like structures in a cultured environment. These cultured epidermal sheets can adhere to skin defects, making them useful for treating thermal burns. Additionally, in recent years, gene therapy has been applied using epidermal keratinocyte stem cells isolated from patients with congenital skin conditions. By introducing normal genes, these cultured epidermal sheets are modified to have normal functions and transplanted for treatment.

In this way, the study of human epidermal keratinocyte stem cells has successfully translated cellular biology advancements into clinical applications, leading the field of regenerative medicine using stem cells.

Dr. Munenori Matsuzawa, Chief Medical Officer, Aoyama Medical Clinic.

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