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標題: | 探討利用幹細胞結合生醫材料(蠶絲蛋白為基質和多醣類)應用於心肌梗塞之心肌再生 Cardiac repair achieved by bone marrow mesenchymal stem cells/silk fibroin/hyaluronic acid patches in a rat of myocardial infarction model |
作者: | Nai-Hsin Chi 紀乃新 |
指導教授: | 王水深,楊偉勛 |
關鍵字: | 蠶絲蛋白摻和材料,間葉幹細胞,心肌分化, Heart,Cardiac tissue engineering,Mesenchymal stem cell,Silk fibroin hybrid patches, |
出版年 : | 2013 |
學位: | 博士 |
摘要: | 心肌梗塞是心衰竭的首要原因,會造成心肌損傷、心組織逐漸喪失及左心室功能受損等。為了修補受損的心肌,有許多動物或臨床實驗正在研發各種骨髓間葉幹細胞治療技術如冠狀動脈內注射以及心肌內注射。雖然許多動物實驗已顯示骨髓間葉幹細胞療法能減少心肌梗塞區域大小、增強心臟功能,但臨床研究中對其增加左心室功能以及修復梗塞的成效仍有爭議。不同研究中骨髓間葉幹細胞療法的相異結果,可能肇因於植運入的骨髓間葉幹細胞在梗塞處微環境內存活率過低。為了增加骨髓間葉幹細胞療法對心肌梗塞的療效,發展一種能協助修補心臟的全新生物材料(如水凝膠或細胞補片),來增加骨髓間葉幹細胞的存活率或促進梗塞心臟血管新生等,是非常值得投注研究的。
生物系統中,蛋白質及聚醣類對於細胞活性及分化扮演很重要的角色,尤其對於細胞間質的合成與細胞分化。本研究使用新的方法將蠶絲蛋白(Silk Fibroin,SF)與幾丁聚糖(Chitosan,CS)和玻尿酸(Hyauronic acid, HA)使用噴霧乾燥的方式製備成微粒再以壓錠的製程製備薄膜,以再生醫學觀念將間葉幹細胞誘導分化後植入心肌壞死部位。骨髓間質幹細胞(bone marrow mesenchymal stem cell, BMSC)/絲素蛋白(SF)/玻尿酸(HA,與前者合稱SH)補片被植入心肌梗塞的老鼠心臟中,以研究其促進左心室重塑及修復的效力。共45隻老鼠被分成四組:假手術組、MI(心肌梗塞,利用冷凍傷害技術來誘導)、SH、BMSC/SH(在心肌梗塞的心臟中分別植入SH、或BMSC/SH補片)。植入後八週,SH及BMSC/SH兩組的補片保持完整、與心肌梗塞區域接合良好、且其引起的免疫反應分別為零與極少;而心肌梗塞組則出現劇烈的發炎反應。SH組在心肌梗塞區域表現出修補效力。和心肌梗塞組的梗塞處做進一步比較,BMSC/SH組能大幅增加左心室壁的厚度、有效運送BMSC、大幅減少細胞凋亡、大幅促進血管新生、刺激各種旁泌因子如血管內皮生長因子。綜合上述研究結果,使用BMSC/SH修復心肌梗塞的心臟,能同時顯現蠶絲蛋白補片之生物活性、以及骨髓間葉幹細胞為基礎之治療的好處。 Cardiac tissue engineering aims at providing contractile heart muscle constructs for replacement therapy in vivo. At present, most cardiac tissue engineering attempts utilize heart cells from embryonic chicken and neonatal rats and scaffold materials bone marrow mesenchymal stem cells/silk fibroin/hyaluronic acid (BMSC/SH) patches were implanted into myocardial infarction (MI) rat hearts to investigate the efficacies of them on enhancing left ventricular (LV) remodeling and cardiac repair. 45 rats were divided into four groups: Sham, MI (MI hearts, induced by a cryo-injury technique), SH and BMSC/SH (MI hearts with implantations of SH and BMSC/SH patches, respectively). After eight weeks of post-implantation, the patches for the SH and BMSC/SH groups were intact and well adhered on the MI zones with no and minor immunological responses, respectively, examined by a CD68 marker, while severe inflammation on the zones was observed for the MI group. The SH group showed the efficacy of cardiac repair on MI zones. Moreover, BMSC/SH group significantly improved the wall thickness of LV, assessed by echocardiography, and had high viability of delivery BMSC, largely reduced apoptosis, significantly promoted neo-vascularization and stimulated the secretions of various paracrine factors such as VEGF, examined by real-time PCR, in MI zones compared with those of the SH and MI groups. In conclusion, the therapeutic efficacies of using BMSC/SH patches for repairing MI hearts were demonstrated by showing the advantages of both bioactive SH patches and BMSC-based therapy. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63082 |
全文授權: | 有償授權 |
顯示於系所單位: | 臨床醫學研究所 |
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