真皮乳头细胞促毛发生长和黑素生成的分子调节机制研究进展

越来越多的证据显示真皮乳头细胞(DPC)是毛囊周期性更新的组织中心。一方面它通过旁分泌的方式分泌大量的细胞因子,刺激隆突区上皮干细胞和黑素细胞干细胞(MeSC)分化、增殖和移行,启动毛发生成。另一方面DPC通过调节干细胞的微环境,譬如真皮乳头的大小、真皮乳头与隆突区的距离以及毛囊隆突区周围的淋巴引流与神经支配等协调完成对毛发生长周期的调节。最新研究显示DPC至少有4个细胞亚群,分别诱导单谱系瞬时扩增上皮细胞形成多层同心圆排列的毛干与毛鞘。还发现持续的心理应激可导致支配隆突区的交感神经过度活跃,交感神经末梢释放大量的去甲肾上腺素可诱导MeSC快速增殖,导致MeSC库耗竭和毛干色素脱失。通过对DPC促毛发生长和黑素生成的分子调节机制的认识,有望在体外大规模培养DPC用于细胞移植治疗人类秃发疾病。

Updated Molecular Regulation of Hair Growth and Pigmentation by Dermal Papilla Cells

There is growing evidence that dermal papilla cells(DPCs)act as the organizing center to induce the cyclic hair regeneration.On one hand,DPCs secrete cytokines or growth factors to regulate the differentiation,proliferation,and migration of epithelial stem cells(EpSCs)and melanocyte stem cells(MeSCs)residing in the bulge region.On the other hand,DPCs manipulate the microenvironment(also termed as niche)for both EpSCs and MeSCs,such as the size of dermal papilla,the distance between dermal papilla and the bulge region,and the lymphatic drainage and sympathetic nerve innervation surrounding the bulge region,thereby orchestrating the cycling hair growth.Recent studies have demonstrated at least four subpopulations existing in dermal papillae,which induce the unilineage transit-amplifying epithelial cells to form the concentric multilayers of hair shafts and sheaths.In addition,emerging study has indicated that sustained psychological stress potentially leads to hyperactivation of the sympathetic nerves that innervate the bulge region.The large amount of norepinephrine released by the nerve endings forces MeSCs to rapidly and abnormally proliferate,resultantly causing the depletion of MeSC pool and the loss of hair pigment.Understanding the molecular regulation of hair growth and pigmentation by DPCs holds substantial promise for the future use of cultured DPCs in vitro to treat hair loss.