低频电磁场在表皮干细胞定向分化形成毛囊结构过程中的作用研究

Several studies have showed that low frequency electromagnetic fields (EMF) can promote cell proliferation or differentiation, but the effects of low frequency EMF on the formation of functional structure do not be yet reported. And how to recover the functional structure of wound is always a clinical problem that needs to be solved in the next years. Based on the evidences from our and others’ previous experiment studies, we will made several different animals models to observe the effects of low frequency EMF on hair follicle germ tissue formation, hair follicle growth and hair growth cycle and to discuss the role of low frequency EMF on epidermal stem cells in the process of hair forming and hair growth cycle. Meanwhile, we will also analyze the signal molecules expression such as BMP, β-catenin, c-Myc in epidermal stem cells and its microenvironment in those models which exposed to low frequency EMF. The different of those signal molecules dynamic spatiotemporal expression will help us to clear the relationship between the BMP signaling pathway and the Wnt/β-catenin pathway, and to confirm molecular mechanism of low-frequency electromagnetic field on hair follicle regeneration. Thus, the current studies, which attempt to exhibit strong evidence to show the effects and molecular mechanism of the low-frequency electromagnetic fields on hair organ regeneration and epidermal stem cells in vivo, can provide a theoretical basis for further study and clinical.

低频电磁场能促进多种细胞增殖或分化，但是否能促进功能性结构形成目前尚未见相关报道。鉴于皮肤创面的功能性愈合是亟待解决的临床问题，本课题在前期实验研究的基础上，通过不同的模型，观察低频电磁场对毛囊胚芽形成、毛囊发育、毛发生长周期的影响，并分析低频电磁场对表皮干细胞的增殖、分化、迁移等的影响在形成毛囊结构中的作用，探讨低频电磁场对表皮干细胞形成毛囊结构的影响；同时，在毛囊胚芽形成、发育、维持更新模型中，检测BMP、β-catenin、c-Myc等多种信号分子在表皮干细胞及其微环境中时空表达差异，分析低频电磁场调控表皮干细胞及其微环境的BMP信号通路与Wnt/β-catenin信号通路之间的动态协调关系，探讨低频电磁场影响表皮干细胞形成毛囊结构的分子机制。通过以上研究，旨在较全面评价低频低频电磁场对表皮干细胞诱导形成毛囊结构的作用，为临床使用低频电磁场用于促进皮肤附属器结构形成奠定理论基础。

在临床应用和基础实验中，低频电磁场促进创面愈合已得到证实，但是否能促进创面愈合过程中形成功能性结构未见有关报道。本项目选择毛囊胚芽、毛发再生、毛发生长周期模型，研究低频电磁场在表皮干细胞诱导形成毛囊结构过程的影响。研究结果显示，在促进表皮干细胞移植后的创面愈合过程中，低频电磁场干预促进了毛囊样的结构形成；在表皮干细胞移植后的裸鼠毛发再生模型中，通过重建表皮干细胞向毛囊分化微环境，可诱导形成毛囊胚芽等皮肤附属结构，低频电磁场干预后，增强组织工程皮肤的再生，同时促进了毛囊胚芽的发育形成毛囊样结构；同时，实验数据亦提示低频电磁场促进表皮干细胞的分化诱导毛囊的再生是通过增强毛乳头细胞的增殖和毛发诱导能力而实现的。为了探索低频电磁场对毛囊生长周期的影响，课题组通过实验发现，低频电磁场可以促进毛囊的生长，该作用与低频电磁场增强毛发生长期毛发内根鞘内的角质化细胞生长因子表达密切相关；同时，在促进毛囊生长过程中，低频电磁场促进了VEGF、PDGF等因子表达。在毛囊再生、毛发生长期过程中，低频电磁场增强BMP、β-catenin的表达，但并未改变BMP、β-catenin的生理表达规律。通过以上研究，较全面评价低频电磁场对表皮干细胞诱导形成毛囊结构的作用；研究结果可以促进低频电磁场在因创伤导致的疤痕性脱发方面开展深入研究，同时为低频电磁场联合表皮干细胞移植治疗斑秃等脱发提供了临床应用依据。