Abstract
A specialized population of cells residing in the hair follicle is quiescent but shows pluripotency for differentiating into epithelial-mesenchymal lineage cells. Therefore, such cells are hoped to be useful as implantable donor cells for regenerative therapy. Recently, it was reported that intracellular delivery of TAT-VHL peptide induces neuronal differentiation of skin-derived precursors. In the present study, we successfully isolated multipotent stem cells derived from the epidermis of elderly humans, characterized these cells as being capable of sphere formation and strong expression of nestin, fibronectin, and CD34 but not of keratin 15, and identified the niche of these cells as being the outer root sheath of the hair follicles. In addition, we showed that TAT-VHL peptide induced their neuronal differentiation in vitro, and confirmed by fluorescence immunohistochemistry the neuronal differentiation of such peptide-treated cells implanted into rodent brains. These multipotent nestin-expressing stem cells derived from human epidermis are easily accessible and should be useful as donor cells for neuronal regenerative cell therapy.
Highlights
The epidermis in humans is a mutilayered epithelium composed of hair follicles, sebaceous glands, and interfollicular epidermis between the orifices of the hair follicles [1]
A specialized nestin-positive cell population residing in the hair follicle has the self-renewing capacity to form spheres and has the potential as multipotent stem cells to differentiate into cells of the the epithelial lineage, and mesenchymal lineage [2]
It has been suggested that the major source of hair follicle stem cells originate from the hair follicle bulge region [8,9], and nascent blood vessels in the skin were shown to arise from these cells [10]
Summary
The epidermis in humans is a mutilayered epithelium composed of hair follicles, sebaceous glands, and interfollicular epidermis between the orifices of the hair follicles [1]. A specialized nestin-positive cell population residing in the hair follicle has the self-renewing capacity to form spheres and has the potential as multipotent stem cells to differentiate into cells of the the epithelial lineage, and mesenchymal lineage [2] This specialized cell population is located in the upper, middle, and lower parts of hair follicles in mice [3], whereas it resides in the outer root sheath of hair follicle below the sebaceous glands in humans [2,4]. Both fibronectin and CD34 have never been simultaneously examined as stem cell markers
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