摘要: | 哺乳類動物毛囊的構造、發育及生長相當複雜,需要透過密切的上皮-間質交互作用 (epithelial-mesenchymal interaction)。來自表皮及真皮的不同訊號,在適當的時間出現,進而造成表皮及真皮的交互作用。在毛囊發育、生長、毛囊週期及病理變化中,毛囊裡特化的間質細胞,即真皮乳突細胞(dermal papilla),扮演重要角色。例如在胚胎發育中,真皮部位形成真皮乳突結構,乳突細胞與表皮的複雜作用中,逐漸誘導表皮向真皮生長並分化成毛囊。過了胚胎時期,可以利用顯微解剖所得的真皮乳突適當地移植到表皮下方,可以在後天誘導表皮朝向毛囊分化,再生毛囊。而病態變化中,例如圓形禿(alopecia areata)及雄性禿(androgenetic alopecia) ,在許多的研究中也顯示,真皮乳突細胞的功能受到影響,進而造成掉髮。低能量可見光或近紅外光的治療,或稱為低能量光線治療(low level light therapy),近年來已在研究及臨床應用上變成一個相當重要的議題與研究領域。低能量雷射在臨床已有重要的治療應用,有別於破壞性的高能量雷射,治療機轉主要是靠直接生物調控 (biomodulation)的方式。當前研究顯示,低能量光線治療可以促進傷口癒合、促進皮膚黑色素細胞再生、保護甲醇引起之視神經傷害、減低大腦之神經傷害、促進幹細胞分化。人體細胞如何透過光受體去感受環境的光訊號,進而達到特定的生物效應,這方面的研究正在起步中。美國食品藥物管理局(FDA)近年來已經核准使用低能量雷射(LaserComb)作為促進頭髮生長之用,但詳細之作用機轉仍未明。我們的假說是,低能量光線可能是透過調控真皮乳突細胞,間接調控上皮-間質交互作用,來達到生髮及保護落髮的效果。我們以發光二極體(light emitting diode, LED)為光源,初步實驗觀察到發光二極體可以促進毛囊乳突細胞的生長,及減低毛囊乳突細胞的細胞凋亡。在此研究中,我們將研究發光二極體促進毛囊乳突細胞生長和對抗細胞凋亡的的機轉。我們也將建立模型,探討發光二極體對毛囊表皮和間質細胞交互作用的影響。短期內著重於研究毛囊真皮乳頭細胞和外根鞘細胞在發光二極體作用下之行為變化。長期希望能夠探討促進毛囊生長,及人體如何感受到環境中的光線而做出反應的分子機轉。將來希望透過與相關工程研究所合作,建構新的治療性光源應用在毛髮疾病之治療,以此為基礎,希望將來可以應用在其他疾病的治療。The structure, development and growth of hair follicles are very complex and depend largely on intimate epithelial-mesenchymal interaction. The signals from both the epidermis and dermis contribute to the epidermal and dermal interaction. In the concept of follicular development, hair growth, hair cycle, and pathological conditions, the mesenchymal cells of hair follicle, named dermal papilla cells, play a pivotal role. For example, in the embryonic stage, the dermal cells condense themselves into dermal papillae, inducing overlying epidermal cells to bud downward to the dermis and further differentiate into follicular structures under the guidance of dermal papillae. In adult life, microdissected dermal papillae have been demonstrated to be capable of inducing hair follicle neogenesis after being appropriately implanted beneath the epidermis. In pathological conditions, such as alopecia areata and androgenetic alopecia, a lot of evidences have suggested impaired function of dermal papilla cells leads to hair loss. The low energy visible or near infrared light treatment, or so called low level light therapy (LLLT), has gained much popularity both in lab researches and clinical applications in recent years. Different from the destructive high energy laser, low level light therapy exerts its effect through direct biomodulation. It has been shown that the low level light therapy is able to promote wound healing, to enhance melanocyte regeneration, to prevent optic nerve injury caused by methanol, to protect central nervous system from injuries, and to facilitate stem cell differentiation. The mechanism of the biological effects of low level light therapy, however, has not been investigated in detail. FDA has recently approved the use of low level laser (LaserComb) in hair loss treatment, with the underlying mechanism not clearly clarified. Our hypothesis is that low level light may reach the clinical effect of hair growth via the interaction with dermal papilla cells to modulate epithelial-mesenchymal interaction. Using the light emitting diode as a new light source, we observed that light emitting diode irradiation promotes the growth and reduces the apoptosis of the dermal papilla cells. In this research, we aim to investigate the mechanisms underlying the growth promotion and anti-apoptosis associated with light emitting diode irradiation. We also plan to set up an in vitro model to investigate the influence of the light emitting diode irradiation on the follicular epithelial-mesenchymal interaction. The short term aim is to characterize the behavior of DP and outer root sheath cells under light emitting diode irradiation. The long term goal is to shed light on the associated molecular pathways regarding light emitting diode irradiation and to construct a new therapeutic light source that can be applied to the treatment of hair diseases. 研究期間:10103 ~ 10207 |