Hair growth stimulated by conditioned medium of adipose-derived stem cells is enhanced by hypoxia: evidence of increased growth factor secretion.

Adipose-derived stem cells (ADSCs) and their secretomes mediate diverse skin-regeneration effects, such as wound-healing and antioxidant protection, that are enhanced by hypoxia. We investigated the hair-growth-promoting effect of conditioned medium (CM) of ADSCs to determine if ADSCs and their secretomes regenerate hair and if hypoxia enhances hair regeneration. If so, we wanted to identify the factors responsible for hypoxia-enhanced hair-regeneration. We found that ADSC-CM administrated subcutaneously induced the anagen phase and increased hair regeneration in C(3)H/NeH mice. In addition, ADSC-CM increased the proliferation of human follicle dermal papilla cells (HFDPCs) and human epithelial keratinocytes (HEKs), which are derived from two major cell types present in hair follicles. We investigated the effect of hypoxia on ADSC function using the same animal model in which hypoxia increased hair regrowth. Forty-one growth factors in ADSC-CM from cells cultured under hypoxic or normoxic conditions were analyzed. The secretion of insulin-like growth factor binding protein (IGFBP)-1, IGFBP-2, macrophage colony-stimulating factor (M-CSF), M-CSF receptor, platelet-derived growth factor receptor-beta, and vascular endothelial growth factor was significantly increased by hypoxia, while the secretion of epithelial growth factor production was decreased. It is reasonable to conclude that ADSCs promote hair growth via a paracrine mechanism that is enhanced by hypoxia.