2015-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/656954摘要：肝硬化（liver cirrhosis) 一直是國人常見的疾病，其所引發的肝癌更是躍居於前十大死因之 一。當肝臟長期處於在發炎狀態下，持續地產生發炎物質將會刺激肝臟内的星狀細胞(tepatic stellate cells, HSCs)處於高度活躍（activation)狀態，不僅將星狀細胞型態從星狀轉變成 纖維狀，也會產生大量的細胞外基質（extracellular matrix, ECM)堆積於肝臟組織，使得纖 維增生與分解失去平衡而形成肝纖維化（liver fibrosis)。肝纖維化過程被認為是屬於一個 變盪的過程也被認為是一個可逆的反應。因此積極的去尋找一個嶄新且具有治療潛力的抗纖 維化（anti-fibrosis)策略乃刻不容緩。近年來幹細胞療法（stem cell therapy)已被廣泛的 研究於動物與臨床試驗上其結果也顯示具有分化免疫調節與修復組織能力。更進一步的非細 胞療法(non-cell based therapy)研究中也發現由幹細胞所生產的細胞液裡含有許多豐富的 生長因子與細胞激素具有治療效果。當前胞外小體療法（exosome therapy)被提出可能具有 治療潛能可以修復受傷的組織。所謂的胞外小體是細胞所分泌的囊泡並攜帶著細胞訊息參與 細胞間通訊。因此在此研究中我們計晝從臍帶血漿(umbilical cord plasma)中提取胞外小體 並注射到肝纖維化的小鼠動物模式裡並評估其抗肝纖維化能力。更進一步的將胞外小體與初 代星狀細胞與肝細胞（hepatocytes)分別培養來觀察其是否有能力抑制星狀細胞活化與促進 肝細胞增殖的分子機制。我們預期此一研究將有助於減緩肝纖維發展並展望於未來臨床上可 行的治療策略。<br> Abstract: Liver cirrhosis has been a common disease in Taiwan, it caused liver cancer is one of the top ranks in the top ten causes of death. Following liver fibrosis, hepatic stellate cells (HSCs) undergo activation to became fibrogenic cells, highly proliferative, and produce excessive extracellular matrix (ECM) proteins (specific for collagen) to accumulate in liver architecture leading to liver dysfunction. Fibrogenesis is dynamic and reversible process, some researchers have suggested anti-fibrosis strategy is a feasible to attenuating liver fibrosis progression. However, it is important that to development a novelty and safely methods for attenuating liver fibrosis. Recently, whatever animal experimental and clinical study have been demonstrated that stem cell therapy and non-cell based therapy are bring hope for patient with liver fibrosis, because of differentiation ability, immunomodulation, and repair damage tissue/organ. Nowadays, exosome therapy have pointed to the possibility for regenerative medicine, but not found in liver fibrosis. Here, we will plan to isolate exosomes from umbilical cord blood plasma, which contains many growth factors and cytokines. Then, to investigate that therapeutic efficiency of exosomes derived from umbilical cord blood plasma in liver fibrosis mice model induced by CCL4. Further, to address effect of exosomes on primary hepatocytes and hepatic stellate cells. We hope our study will help to elucidate the therapeutic potential of exosomes in novel filed of regeneration medicine.細胞外基質抗肝纖維化胞外小體Extracellular matrixAnti-fibrosisExosomes