Won Chong Hyun, Jeong Yun-Mi, Kang Sangjin, Koo Tae-Sung, Park So-Hyun, Park Ki-Young, Sung Young-Kwan, Sung Jong-Hyuk
Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.
Department of Applied Bioscience, CHA University, Seoul 135-081, Korea.
Int J Mol Sci. 2015 Feb 19;16(3):4379-91. doi: 10.3390/ijms16034379.
Keratinocyte stem/progenitor cells (KSCs) reside in the bulge region of the hair follicles and may be involved in hair growth. Hair follicle dermal papilla cells (HFDPCs) and outer root sheath (ORS) cells were treated with conditioned medium (CM) of KSCs. Moreover, the effects of KSC-CM on hair growth were examined ex vivo and in vivo. A human growth factor chip array and RT-PCR were employed to identify enriched proteins in KSC-CM as compared with CM from keratinocytes. KSC-CM significantly increased the proliferation of HFDPCs and ORS cells, and increased the S-phase of the cell cycle in HFDPCs. KSC-CM led to the phosphorylation of ATK and ERK1/2 in both cell types. After subcutaneous injection of KSC-CM in C3H/HeN mice, a significant increase in hair growth and increased proliferation of hair matrix keratinocytes ex vivo was observed. We identified six proteins enriched in KSC-CM (amphiregulin, insulin-like growth factor binding protein-2, insulin-like growth factor binding protein-5, granulocyte macrophage-colony stimulating factor, Platelet-derived growth factor-AA, and vascular endothelial growth factor). A growth-factor cocktail that contains these six recombinant growth factors significantly increased the proliferation of HFDPCs and ORS cells and enhanced the hair growth of mouse models. These results collectively indicate that KSC-CM has the potential to increase hair growth via the proliferative capacity of HFDPCs and ORS cells.
角质形成干细胞/祖细胞（KSCs）位于毛囊的隆突区，可能参与头发生长。用KSCs的条件培养基（CM）处理毛囊真皮乳头细胞（HFDPCs）和外根鞘（ORS）细胞。此外，还在体外和体内研究了KSC-CM对头发生长的影响。使用人类生长因子芯片阵列和RT-PCR来鉴定KSC-CM中与角质形成细胞CM相比富集的蛋白质。KSC-CM显著增加了HFDPCs和ORS细胞的增殖，并增加了HFDPCs细胞周期的S期。KSC-CM导致两种细胞类型中ATK和ERK1/2的磷酸化。在C3H/HeN小鼠皮下注射KSC-CM后，观察到毛发生长显著增加，体外毛发基质角质形成细胞的增殖增加。我们鉴定出KSC-CM中富集的六种蛋白质（双调蛋白、胰岛素样生长因子结合蛋白-2、胰岛素样生长因子结合蛋白-5、粒细胞巨噬细胞集落刺激因子、血小板衍生生长因子-AA和血管内皮生长因子）。含有这六种重组生长因子的生长因子混合物显著增加了HFDPCs和ORS细胞的增殖，并促进了小鼠模型的毛发生长。这些结果共同表明，KSC-CM有潜力通过HFDPCs和ORS细胞的增殖能力来促进毛发生长。
