2012-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/658818摘要：本研究發展之 MSC/Silk/HA 心肌綴補片，可增進MSC 於MI 心室生存及心肌再生。纖維蛋白膠(Fibrin)，可應用於組織工程及藥物制放。紅血球生成素(EPO)與5-AZA 共同作用下，對MSCs 的生長及心肌分化有促進作用。本研究以Fibrin 膠作為固定MSC/Silk/HA 貼片並以含EPO 的微、奈米粒子delivery EPO 到MI 心室，來增進MSC於MI 鼠及猪心肌之修護。主要研究為轉染GFP 之自體MSC(MSC(G))/SF/HA patches於加入含EPO 的微、奈米粒子後，MI 鼠心肌的修補及心室功能情形。輔以Micro-CT觀察不同時間下(~ 6 星期) ， patches 於MI 老鼠的變化及其他心室參數。MI 猪的研究將類似MI 鼠。本計畫，第一部份製作含有EPO 的Chitosan 微、奈米粒子製備及其於纖維蛋白凝膠之控制釋放研究，in-vitro 探討(1)不同fibrinogen 濃度對fibrin 膠黏度、貼附於組織的能力及對奈米粒子之EPO 控制釋放；(2) 老鼠及猪MSC(G)對SF/HA 的patches的生長及分化的情形(包含MTS，morphology，fibronectin，GATA4…等基因表現)；第二部分in-vivo 探討：MI 鼠在MSC(MSC(G))/SF/HA patches 於加入含EPO 粒子後，心肌功能恢復及paracrine factors…等之研究；藉由MSC(G)、delivery EPO、Micro-CT 觀察…等；進一步瞭解MSC(G)在MI 心肌存活及分化、EPO 效應、patches 完整性…等情形。第三部分為MI 猪體內實驗：加大面積之MSC(G) patches、delivery EPO 對修復MI猪之心肌功能的研究，結果分析類似MI 老鼠。藉此新的研究，對MSC(G) 對MI 猪的心肌修補之mechanism 及functions 深入瞭解，作為臨床測試之的重要前置研究。<br> Abstract: We developed a new MSC/SF/HA cardiac patch which promote remodeling andvascularization of MI rat hearts. Moreover, EPO can promote the proliferations of MSC anscardiomyogenesis of 5-aza inducing MSC. In this study, we will using fibrin gels to fix GFPtransfection MSC,(MSC(G))/SF/HA patches and carry EPO encapsulated chitosan micro- ornanoparticles to further promote the remodeling of rat and pig MI hearts and the relatedmechnisms.The works of the first part of the project will be : (1) preparing EPOencapsulated chitosan NPs, embedded in fibrin gels and characteristics of NPs includingEPO release profiles, (2) an in-vitro study of the proliferations and cardiomyogenesis ofMSC(G) on SF/HA patches. The works of the second part of the project will be: (1) in-vivostudy the efficacy of MSC(G)/SF/HA patches and delivery EPO by NPs on MI hearts of ratsincluding the effects of NPs, survival percentages of MSC(G) in MI hearts, the functionalrecovery of MI hearts, and the morphological changes of the patches observed using varioustechniques, as reported by our publications, and micro-CT after 6 weeks of transplantationof patches. The works of the third part of the project will be MI hearts of pigs (by ligationtechnique) which will be the similar to those of rats except a larger patches. Through thestudy, we can further understand the contributions of MSC on promoting MI heartsremodeling and vascularization and their related mechanisms that can provide importantmessages for pre-clinical study in near future.SF/HA 的patchesChitosan 微奈米粒子紅血球生成素轉染GFP 之自體 MSC心肌再生SF/H patchesChitosan NPEPOGFP transfection MSCregeneration of MI hearts