News Express: UM develops natural oligosaccharides for hair regeneration
新聞快訊：澳大開發天然寡糖生物材料促毛髮再生
澳大團隊開發的全新生物材料誘導小鼠毛髮再生
The new biomaterial developed by the UM team induces murine hair regrowth
澳大開發天然寡糖生物材料促毛髮再生
澳門大學中華醫藥研究院、中藥質量研究國家重點實驗室教授王春明及其研究團隊，聯合南京大學生命科學院教授董磊和溫州醫科大學藥學院教授肖健，研發出一種植物來源的寡糖生物材料（OG6），研究證明將其注射至小鼠皮膚內，可明顯加快毛髮生長。相關研究成果已獲得國家發明專利授權及進入國際專利公告（PCT），並發表於國際材料學頂級期刊Advanced Materials。
人的毛髮具有重要的生理功能。然而，因遺傳、激素水平、情緒壓力等因素造成的脫髮問題，影響全球數千萬人。目前，臨床獲批的藥物少且副作用較明顯；植髮手術價格高，也帶來痛苦。因此，治療脫髮的臨床需求與市場價值巨大。王春明於三年前開啟該研究，現正計劃與企業和臨床機構洽談下一步合作，期望早日進入臨床轉化的快車道，開發新藥上市。他也期望自己能夠成為新藥的第一批使用者。
王春明表示，哺乳動物的毛髮從毛囊中長出，其生長具有週期性，從靜止期到生長期的轉變受局部組織的生理微環境調控。毛囊附近某類免疫細胞數量或某類細胞因子濃度的變化，都可能刺激毛囊生長，但這些變化難以精準控制。在該研究中，團隊優選出一種“纖維素酶”，如同剪刀一般，可將天然藥物蒟蒻來源的葡甘聚糖，從非常大的分子“剪”成比較小的分子片段。從一系列比較小的片段中，研究人員找到一個代號為OG6的寡糖組分，可以精確誘導皮膚中的特定細胞釋放一種名爲“趨化因子”的信號（CCL5）。這個信號如同交通燈，可引導一類名為調節性T細胞的免疫細胞遷移到毛囊周圍，和毛囊幹細胞發生作用，刺激毛囊進入生長期。有趣的是，無論是作為原料的大分子還是酶解同時獲得的其他組分，都不具備OG6的這一特異活性。團隊猜測，這一“剪”，暴露出了寡糖被多糖分子鏈所掩蓋的“隱藏活性”。團隊在使用多種生物學方法驗證了OG6的作用機制後，將OG6注射到褪毛後的野生小鼠及轉基因報告小鼠皮內，觀察到健康的毛髮在注射部位快速新生，且未出現皮膚過敏或任何毒副作用。更為重要的是，OG6在體內最終降解產物是葡萄糖和甘露糖兩種人體內本身存在的物質，預計安全性高。
澳大中華醫藥研究院碩士畢業生殷小雨為研究的第一作者。該項目獲澳門特別行政區科學技術發展基金“澳門重點研發資助計劃”（檔案編號：0001/2021/AKP）、國家自然科學基金委員會“優秀青年科學基金項目（港澳）”（檔案編號：32022088）、深圳市科技創新委員會“深港澳科技計劃（C類）”（檔案編號：SGDX2020110309280301）等支持。全文可瀏覽：https://doi.org/10.1002/adma.202304655。
欲瀏覽官網版可登入以下連結:
https://www.um.edu.mo/zh-hant/news-and-press-releases/presss-release/detail/56471/
UM develops natural oligosaccharides for hair regeneration
A research team led by Wang Chunming, professor at the Institute of Chinese Medical Sciences and the State Key Laboratory of Quality Research in Chinese Medicine of the University of Macau (UM), in collaboration with Dong Lei, professor at the School of Life Sciences of Nanjing University, and Xiao Jian, professor at the School of Pharmaceutical Sciences of Wenzhou Medical University, has developed a new biomaterial based on plant-derived oligosaccharides (OG6). The study shows that injecting OG6 into the skin of mice could markedly accelerate hair growth. The research results are protected by a granted Chinese invention patent and under the Patent Cooperation Treaty (PCT) and have been published in the top international journal Advanced Materials.
Human hair has vital physiological functions. However, hair loss caused by genetic factors, hormone levels, emotional stress, and other factors, affects tens of millions of people worldwide. At present, there are few clinically approved drugs available on the market and the side effects are substantial, while hair transplantation can be costly and painful. The clinical demand and market value of hair loss treatment are therefore considerable. Prof Wang, who initiated the research three years ago, is now discussing future collaboration with companies and clinical institutions to fast-track the clinical translation of the research results and develop a new drug for the market. He also hopes to be one of the first batch of users of the new drug.
According to Prof Wang, mammalian hair grows from hair follicles (HFs) and hair growth is cyclical, with the transition from ‘anagen’ (growth) to ‘telogen’ (rest) phases being regulated by the physiological microenvironment of the local tissues. Changes in the number of certain immune cells or the concentration of specific cytokines can stimulate HF growth, but such changes are difficult to control precisely. In the study, the team optimised an enzyme, which acts like a pair of scissors, to ‘cut’ the large molecules from natural plant-derived glucomannan polysaccharides into smaller oligosaccharides, from which the researchers identified a fraction called OG6. OG6 can specifically induce specific cells in the skin to release a signal called CCL5. The signal acts like a traffic light and leads a type of immune cells called regulatory T cells to migrate towards HFs, interact with the stem cells around HFs, and stimulate HFs to enter the anagen phase. It is interesting to note that neither the large molecules that serve as source material nor the other small fractions obtained from the cutting possess this specific function of OG6. The team speculated that the cutting exposes the ‘hidden activity’ of the oligosaccharides, which is concealed by the polysaccharide chain. After verifying the molecular mechanism of OG6 with multiple biological methodologies, they injected OG6 into the dermal tissue of wild-type and transgenic mice whose hair had been shaved and observed that healthy hairs grew rapidly in situ without skin allergies or toxic side effects. More importantly, OG6 is a safe substance as its final degradation products are glucose and mannose, which are already present in the human body.
Yin Xiaoyu, a master’s graduate of the Institute of Chinese Medical Sciences of UM, is the first author of the study. The research project was supported by the ‘Macao Funding Scheme for Key R&D Projects’ of the Science and Technology Development Fund of the Macao SAR (File no: 0001/2021/AKP), the ‘Excellent Young Scientists Fund (Hong Kong and Macao)’ of the National Natural Science Foundation of China (File no: 32022088), and the ‘Shenzhen-Hong Kong-Macao Technology Research Programme (Type C)’ of the Shenzhen Science and Technology Innovation Commission (File no: SGDX2020110309280301). The full version of the research article can be viewed at https://doi.org/10.1002/adma.202304655.
To read the news on UM’s official website, please visit the following link:
https://www.um.edu.mo/news-and-press-releases/press-release/detail/56471/