- 學位論文
探討飛梭雷射誘導毛囊再生之機轉
The Key Mechanism of Early Anagen Entry Induced by Farxel Laser
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摘要
毛囊具有替人體屏障外界傷害與保溫保濕等複雜且多樣化的功能，是為人體中重最重要的器官之一。它是一個擁有高度自我調控能力的 微小器官，具有毛囊幹細胞與自己的生長週期，其形態也會隨著生長周期而有所變化。因此毛囊本身的生理調控與受刺激後產生的後續反應和修復機制、和環境間的溝通，都已成為再生醫學研究探討重要領域。毛囊在休止期時會受到許多不同的引發因子激發，從而進入生長期，例如傷口、化學物質、光照，等等。熟悉這些因子也被視為能夠掌握促進毛髮生長的關鍵鑰匙。本研究的目標希冀能探索毛囊感受到外界的微小刺激後活化、從休止期提前進入生長狀態的生長期之背後機轉。 我們先前的研究已指出第二代飛梭雷射 Fraxel SR1500 造成的刺激能引誘毛囊提前進入生長期。本研究遂以此作皮膚刺激物，調整能量後，以不會在皮膚留下疤痕的能量，引發接觸性刺激性皮膚炎，刺激毛囊進入生長期。本研究發現，經過刺激之後將引發 TNF-α、IL1 等發炎因子與 VEGF 家族、PDGF 等生長因子表現，並引起嗜中性白血球與巨噬細胞等免疫細胞大量進浸潤囊周圍的區域，同時促使巨噬細胞活化為 M1 與 M2 型。 在經由TNFα 基因剔除鼠、注射 Avastin 與 Zaltrap 抑制 VEGFs、施打 Ly6G 抗體耗竭嗜中性球以及皮下注射 Clodrosme 使巨噬細胞凋亡後，發現 VEGFA、巨噬細胞和其高度分泌的 PlGF 在本雷射刺激誘發毛囊提前進入生長期的實驗中具有促進生長期的效果，也在毛囊上看到這些因子的受器有高表現。 簡言之，本研究確立了一個小鼠皮膚在接受飛梭雷射以一定能量刺激後，能不導致疤痕且促進 VEGFA 提高、巨噬細胞分泌 PlGF，進而使 VEGFA 與 PlGF 協同作用使休止期毛囊進入生長期的實驗模型。
並列摘要
Hair follicle, one of the most important organ in human, is able to keep us warm, moisture and from external injury, which is a miniorgan with high self-regulation ability, an unique lifecycle and fueled by its resident stem cells. Their structure also vary with hair cycle. Thus, the issue about how hair follicle does self-regulation, reacts and repairs itself after injury for physiological growth, communicates with niche microenvironment are worth exploring in regenerative medicine feilds. Follicle will activated by several different initiators in telogen and then enter anagen phase, including chemicals, light, and wound, and these factors are thought to be the key to promote hair growth. This study is aimed at exploring how microenvironment transformed after miniwound, how follicle stem cells reacted to this change and activated, and finally regenerated from telogen to anagen.We used Fraxel SR1500 as irritant to induce irritant contact dermatitis without scarring during telogen phase afetr ajusting energy settings. We found that inflammatory or growth factors like TNF-α, IL1, VEGF family, and PDGF incresed after injury, as well as numerous immune cells infiltrated to the injured area, including neutrophils and macropages activated to M1 or M2 type. We then found that VEGFA, macrophages and PlGF secreted mainly from macropahges may promote early anagen entry by laser according to experiment results depleting TNF-α by transgenic mice, VEGF family by Avastin and Zaltrap, neutrophils by Ly6G antibody, and macrophages by Clodrosome. Our findings indicated that VEGFA increased after Fraxel laser injury and macrophages recuited to wound area followed by secreting PlGF to co-work with VEGFA to incude early anagen entry via VEGFR2 on follicle.
並列關鍵字
Hair follicle stem cells ； Fraxel laser ； Irritant contact dermatitis ； Macrophages ； VEGF ； PlGF ； VEGFR ； Avastin ； Zaltrap ； Clodrosome參考文獻
93. Haur Yueh Lee et al., Cytokines and Chemokines in Irritant Contact Dermatitis. Mediators of Inflammation 2013, 1-7(2013)
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