The outermost layer of the skin – the epidermis – is a rapidly renewing tissue and relies on the regenerative capacity of keratinocytes. Skin grafts using human cultured epidermal cells have been successful in treating patients with severe skin wounds. The notion that the ability to regenerate functional epidermal tissue is an exclusive property of epidermal stem cells is a general assumption in the stem cell biology field. In the February 2 issue of the Journal of Clinical Investigation, Pritinder Kaur and colleagues at the Peter MacCallum Cancer Centre, Australia, demonstrate that both epidermal stems cells and their early, differentiated progeny contribute to rapid epidermal regeneration.
The majority of proliferating epidermal cells, also known as transit-amplifying cells, at the inner-most layer of the skin have a finite life span and undergo rapid terminal differentiation. Therefore it is well accepted that the extensive regenerative capacity of the skin is most likely attributed to the activity of epidermal stem cells.
To determine the cells responsible for rapid epidermal regeneration, Kaur and colleagues separated epidermal stem cells from their progeny and assayed the ability of both cell types to regenerate epidermal tissue in both in vitro and in vivo settings. As expected, keratinocyte stem cells displayed robust regenerative capabilities, but unexpectedly, transit-amplifying cells and early differentiating cells, which are more committed progenitor cells, could also form a fully stratified epidermis under appropriate microenvironmental conditions. The authors also demonstrated that the regenerative capacity of these cell types could be enhanced by exposure to the protein laminin-10/11.
This work presents important new considerations for the expansion of keratinocyte progenitor cell populations for therapies that require large numbers of epidermal cells, such as those required for the treatment of severe wounds such as extensive burns. It may be possible to harness the vast proliferative potential of readily available and accessible keratinocyte progenitors of the skin for cellular therapies, thereby removing the need for difficult and limited stem cell selection.
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