我們實驗室主要利用毛囊為模型,研究幹細胞的調控與組織再生的機轉。我們希望結合生物學的原理與組織工程的方法,發展有效促進毛囊生長的方法。毛囊由皮膚發育而來,上方由其特色的角質細胞構成一立體柱狀的結構,而毛囊的間質細胞 (毛囊乳突細胞)則聚集成團位於毛囊根部。透過毛囊的上皮-間質交互作用 (epithelial-mesenchymal interaction),毛囊可以週期性再生。其週期可分為退化期,休止期與生長期。毛囊在生長期與休止期的體積可以有幾十倍的差異,是生理上體內體積變化最大的組織。毛囊幹細胞位於毛囊角質細胞部位內,毛囊再生有賴於毛囊幹細胞的活化。毛囊也是研究幹細胞調控的重要模型。毛囊進入生長期之後,是體內細胞分裂最快的組織之一,頭髮的生長有賴於毛囊球內的細胞快速分裂,此時毛囊內部會分化出七層不同分化狀的細胞。因為其快速生長的特性,毛囊在受到放射線或化療的傷害後,細胞容易死亡,造成大量掉髮。毛囊幹細胞的調控,特別是毛囊幹細胞如何感受環境的變化而再生新髮,是生物學上有趣的問題。此外毛囊幹細胞的活性減低,會造成禿髮。透過活化與保護毛囊幹細胞,可以促進生髮與減少禿髮。因此毛囊幹細胞的研究,也具有臨床醫學的重要性。我們實驗室的研究著重在:
We employs hair follicles as a model to study how stem cells are regulated and to decipher the principles of tissue regeneration. We aspire to combine biological principles and tissue engineering technology to promote hair growth and to prevent hair loss. The hair follicle, a 3-dimnensional cylindrical miniorgan derived from the skin, is composed of keratinocytes on the top with its characteristic mesenchymal cells, named dermal papilla cells, aggregated at the bottom. The hair follicles are one of the few organs that undergo life-long cyclic growth. Through epithelial-mesenchymal interaction, hair follicles cyclically transit from catagen (regressing phase) through telogen (resting phase) and back to anagen (growing phase). It is the tissue that exhibits the largest volume change in the physiological state within the body, with dozens of times increase of volume from resting to growing phase. Hair follicle stem cells are harbored in the keratinocyte compartment, and their activation fuels the regeneration of hair follicles from the resting phase. In the growing phase, hair follicles have the fastest cell division in the body to support continuous hair shaft elongation. In this phase, hair follicle keratinocytes also exhibit a high degree of cell plasticity, differentiating into seven distinct cell layers within the hair follicle. Because of its rapid growth characteristics, growing hair follicles are highly sensitive to radiation or chemotherapy, and extensive hair loss can occur. The regulation of hair follicle stem cells, especially how hair follicle stem cells sense environmental changes for regeneration, is an interesting question in biology. On the other hand, studying hair follicle stem cells and their injury response is also of clinical significance. When the activity of hair follicle stem cells is compromised or the hair follicles are damaged, alopecia can develop. By activating hair follicle stem cells and promoting self-repair after injury, we can promote hair growth and prevent hair loss. Our laboratory research focuses on:
1. How do tissue microenvironment (microniche), systemic factors (macroniche) and the external environment (macroniche) regulate hair follicle stem cells?
2. How do individual hair follicle cells in this three-dimensional miniorgan communicate and coordinate with other cells to achieve tissue regeneration and degeneration?
3. How do growing hair follicles repair themselves after injury to avoid entering into catagen (regressing phase)?
4. How is the hair cycle regulated?
5. How to regenerate new hair follicles once they are lost?
6. Regeneration of other tissues and cells, including skin, cornea, pigment, etc.
7. Tissue engineering for tissue regeneration.