Thymosin beta4 increases hair growth by activation of hair follicle stem cells.

Thymosin beta4, a 43-amino acid polypeptide that is an important mediator of cell migration and differentiation, also promotes angiogenesis and wound healing. Here, we report that thymosin beta4 stimulates hair growth in normal rats and mice. A specific subset of hair follicular keratinocytes in mouse skin expresses thymosin beta4 in a highly coordinated manner during the hair growth cycle. These keratinocytes originate in the hair follicle bulge region, a niche for skin stem cells. Rat vibrissa follicle clonogenic keratinocytes, closely related, if not identical, to the bulge-residing stem cells, were isolated and their migration and differentiation increased in the presence of nanomolar concentrations of thymosin beta4. Expression and secretion of the extracellular matrix-degrading enzyme matrix metalloproteinase-2 were increased by thymosin beta4. Thus, thymosin beta4 accelerates hair growth, in part, due to its effect on critical events in the active phase of the hair follicle cycle, including promoting the migration of stem cells and their immediate progeny to the base of the follicle, differentiation, and extracellular matrix remodeling.