2012-05-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/649394摘要：幹細胞生物學，發育生物學及組織工程的進步對於臨床的組織及器官再生，帶來新的契機及希望。透過毛囊再生以治療禿髮也是其中一個受到重視的發展。毛囊結構上可分成兩個部分，包括由角質細胞所構成的上皮部分及真皮乳突細胞所構成的間質結構。毛囊的形態發生依賴細緻且動態的上皮-間質交互作用，而類似的交互作用也對其他上皮器官發育相當關鍵。為了治療臨床上的禿髮，在同一位病人身上需要新生數百至數千個新的毛囊。因此，可取得有限數量的毛囊幹細胞及真皮乳突細胞在移植前需要大量培養擴展。我們和其他的研究者發現，培養過的真皮乳突細胞若聚集成立體的多細胞團，可以有效率地誘導角質細胞新生毛囊(Young TH et al. Biomaterials 2008 & 2009)。但毛囊幹細胞經過培養後，會失去新生毛囊的能力，因而減損毛囊再生的效率。我們先前的研究顯示，在具有適當基材及培養條件的誘導下，離散的角質細胞及真皮乳突細胞可以有效率地進行試管內形態發生，生成毛囊樣雛形器官。這樣的條件可以誘導原本不易新生毛囊的角質細胞再生毛囊 (Yen CM et al. Biomaterials 2010)。根基於我們先前的研究結果，我們在此計畫中嘗試解決目前進行大量毛囊再生所遇到的困難。此計畫有三個目標：(1)發展以生醫材料為基材的培養系統以維持毛囊幹細胞的毛囊再生能力 (2) 發展試管內形態發生的方法，大量誘導毛囊幹細胞生成毛囊樣雛形器官(3) 測試毛囊樣雛形器官的安全性及新生毛囊的效率及效果 。<br> Abstract: With the advent of stem cell biology, developmental biology and tissue engineering, there are progresses and new hopes in translating these results for potential clinical tissue/organ regeneration including hair follicles (HFs). HF is composed of an epithelial part of keratinocytes and a mesenchymal structure of dermal papilla (DP) cells. HF morphogenesis depends on a delicate dynamic epithelial-mesenchymal interaction (EMI) which has been shown to be key to the organogenesis of many epithelial organs. For the clinical treatment of hair loss, hundreds to thousands for HFs are usually needed be regenerated in a single patient. Due to the limited numbers of HF stem cells and DP cells that can be procured, both HF stem cells and DP cells should be expanded in vitro before they can be transplanted back to the patient. We and other groups have showed that HF neogenesis from keratinocytes can be efficiently induced by DP cells when the DP cells are cultured into multicellular aggregates (Young TH et al. Biomaterials 2008 & 2009). However, cultured HF stem cells quickly lose the inherent trichogenic ability when they are expanded in vitro, hence leading to a poor regenerative efficiency. We have shown that through the use of specified culture substrata in defined conditions, in vitro HF morphogenesis from dissociated keratinocytes and DP cells into HF-like organ germs can be facilitated and the trichogenic ability of keratinocytes can be enhanced to grow new hairs (Yen CM et al. Biomaterials 2010). Based on our prior results, we aim to bridge the gaps between the current bench work and potential clinical application of HF regeneration. Three aims are proposed in this project: (1) To develop biomaterial substratum-based culture systems to preserve the trichogenic ability of hair follicle stem cells. (2) To develop methods for scalable production of HF-like organ germs by biomaterial-facilitated in vitro morphogenesis from HF stem cells. (3) To examine the safety of HF-like organ germs and their efficiency and efficacy for HF regeneration.毛囊幹細胞毛囊再生真皮乳突生醫材料上皮-間質交互作用試管內形態發生hair follicle stem cellhair follicle regenerationdermal papillabiomaterialepithelial-mesenchymal interactionin vitro morphogenesis