2013-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/689042摘要：間質幹細胞為目前廣泛研究之成體幹細胞且已有多項臨床應用技術發展中。然而，由於正常生理狀況下之幹細胞微環境尚未釐清，目前尚無法確立無血清之間質幹細胞培養條件，進而限制了其臨床應用之發展。本團隊先前研究證實細胞自身之硫酸乙醯肝素&#37238;在骨髓間質幹細胞自我更新及遷移中扮演重要角色。在本研究中，我們希望驗證：（1）硫酸乙醯肝素&#37238;是否藉由調控細胞外之硫酸乙醯肝素蛋白多醣促進自我更新之訊息傳遞或抑制對抗自我更新之訊息路徑；（2）硫酸乙醯肝素&#37238;是否參與細胞核內之染色質組態修飾，進而調控相關基因表現。近期研究顯示骨髓間質幹細胞在正常生理環境中會參與骨持衡作用。因此我們假設硫酸乙醯肝素&#37238;可藉由調控間質幹細胞命運，影響骨之持恆與再生。此研究結果將可使我們更了解微環境對間質幹細胞之影響，並可進一步發展控制體內間質幹細胞增生及分化之策略。此外，也可針對調控硫酸乙醯肝素&#37238;或硫酸乙醯肝素醣胺聚醣研發新的骨修復治療方式。<br> Abstract: Mesenchymal stem cells (MSCs) have been one of the most studies stem cells of adult sources and various clinical applications has been envisioned and under development. However, unsatisfactory serum-free culture condition due to the lack of knowledge over the physiological stem cell niche limits the clinical applications. Our previous study demonstrated that the cell autonomous HPSE1 plays a role on the self-renewal and migration of marrow MSCs. In this research proposal, we aim to investigate the detailed molecular mechanisms how heparanase involves in the maintenance of the stemness of marrow MSCs by testing two of our hypothesis: (1) heparanase might modulates cell-surface and/or extracellular HSPGs and in turn promote the signalings for self-renewal or inhibit the signalings that antagonize self-renewal of MSCs; and (2) heparanase could participate in the maintanence of self-renewal of MSCs via this intranuclear mechanism, involve in the chromatin signature modulation, and in turn the gene expression profile. Recent studies indicated that the physiological role of mouse marrow MSCs is limited for bone homeostasis. Therefore, we further hypothesize that heparanase plays a role in bone homeostasis and regeneration via the modulation of the fate of MSCs. The results of this proposed study would lead us to a better understanding about niche microenvironment for MSCs biology through which we may develop novel strategies to modulate MSCs proliferation and differentiation in vivo. Furthermore, a novel therapeutic strategy targeting heparanase/heparan sulfate glycosaminoglycans might be developed for bone health and bone repair.骨髓間質幹細胞硫酸乙醯肝素蛋白多醣硫酸乙醯肝素醣胺聚醣自我更新細胞遷移胞外基質骨質修復marrow mesenchymal stem cellsMSCsheparan sulfate proteoglycansHSPGsheparan sulfate glycosaminoglycansHS-GAGsself-renewalmigrationbone repair