自體間質幹細胞、輔酶Q10及富含血小板纖維對豬急性心肌梗塞的應用

Application of Autologous Mesenchymal Stem Cells, Coenzyme Q10 and Platelet-rich Fibrin for Acute Myocardial Infarct in Porcine

林昇全(Sheng-Chuan Lin)

指導教授 ： 許岩得 ； 郭宗甫

國立屏東科技大學/農學院/熱帶農業暨國際合作系所/博士(2012年)

https://doi.org/10.6346/NPUST.2012.00211

摘要

摘 要

學號：P9822001
論文題目：自體間質幹細胞、輔酶Q10及富含血小板纖維對豬急性心肌梗塞的應用
總頁數：104
學校名稱：國立屏東科技大學 系別:熱帶農業暨國際合作系
畢業時間及摘要別：100 學年度第二學期博士學位論文摘要
研究生：林昇全 指導教授：許岩得; 郭宗甫

論文摘要內容：
幹細胞療法是“更換或再生細胞，使組織或器官的正常功能恢復或建立的過程”。幹細胞療法有可能解決器官短缺的問題。再生醫學涉及的幹細胞使用，包括注射幹細胞或先驅細胞（細胞療法）的臨床治療方法，幹細胞研究的臨床應用變得越來越重要。尤其是關於培育幹細胞，或分化成包括心肌細胞，神經細胞，軟骨細胞，肝，腎細胞，肺上皮細胞等。在這研究中我們分離，培養和應用間質幹細胞在中型動物（豬，貓，狗等）的再生醫學治療應用，希望建立再生醫學的動物治療模型。細胞療法可能帶來新的機會，提高幹細胞通過轉分化成心肌細胞，以取代或修復受損的組織或細胞。我們誘導人工急性心肌梗塞模型並以自體性的幹細胞治療模式。在左冠狀動脈第一分枝後的位置進行30分鐘的人工閉塞，心肌細胞發生不可逆轉的損害。實驗數據證明，細胞療法有可能修復受損的心肌，以減少急性心肌梗塞的持續傷害。實驗是利用間質幹細胞的性能來修補受損的細胞，並期待以Q10來增加幹細胞的性能及活性。富含血小板纖維(platelet-rich fibrin, PRF) 是由血液中分離出的血液延生材質，PRF含有大量的生長因子及cytokines。實驗中我們以單一步驟的分離方法萃取出PRF 並進行人工急性心肌梗塞的植入治療，結果顯示PRF 可以有效的改善心肌梗塞的左心功能表現。Q10是粒線體進行呼吸作用產生ATP所需的輔脢，Q10已被證實可改善慢性心衰竭病患的存活時間。腎臟疾病進展的特點是腎小球硬化和腎間質纖維化的發展。幹細胞生物學的進步已經幫助設計幹細胞作為治療手段，加快組織修復。在臨床案例研究中我們採用自體幹細胞注入腎動脈內停止或減慢貓慢性腎臟病纖維化。實驗結果顯示，間質幹細胞,Q10和PRF的治療明顯改善心臟左心功能EF及FS的表現，減少心肌因梗塞造成的纖維化面積。間質幹細胞在腎小球硬化和腎間質纖維化的發展可以阻止纖維化進程，改善腎功能。

關鍵詞: 再生醫學、間質幹細胞、急性心肌梗塞、慢性腎臟病、纖維化

關鍵字

再生醫學 ； 間質幹細胞 ； 急性心肌梗塞 ； 慢性腎臟病 ； 纖維化

並列摘要

Abstract
Student ID: P9822001
Title of Thesis: Application of Autologous Mesenchymal Stem Cells、
Coenzyme Q10 and Platelet-rich Fibrin for Acute Myocardial Infarct in Porcine
Total Page: 104
Name of Institute: Department of Tropical Agriculture and International Cooperation, National Pingtung University of Science and Technology.
Graduate Date: July, 2012 Degree Conferred: Ph.D.
Name of Student: Sheng-Chuan Lin Advisor: Professor Yan-Der Hsuuw
Professor Tzong-Fu Kuo
The Contents of Abstract in This Thesis:
Stem cells therapy is the “process of replacing or regenerating cells, tissues or organs to restore or establish normal function”. Stem cells therapy also has the potential to solve the problem of the shortage of organs. Medicine refers to a group of biomedical approaches to clinical therapies that may involve the use of stem cells, including the injection of stem cells or progenitor cells (cell therapies). Stem cell research application has gotten more and more important achievements now. Especially with regard to the methods to cultivate stem cells or to obtain progenitor cells including myocardiocyte, nerve cells, chondrocytes, hepatocytes, renal cells, lung epithelial cells, etc. In this study, we isolated, cultivated and applied the mesenchymal stem cells in middle animals (pig, cat and dog) regenerative medicine. Wish to create the regenerative medicine therapy models of middle animals. CoQ10 is widely distributed in animals and humans. It plays an important role in cellular energy production in the mitochondrial respiratory chain. CoQ10 has been demonstrated to have a potential role in the prevention and treatment of heart diseases by improving cellular bioenergetics. Cardiogenic shock is a state of inadequate tissue perfusion induced by cardiac disorders. The incidence of cardiogenic shock complicating acute myocardial infarction ranges from 5% to 10% in human being. The most frequent cause of acute MI is associated with myocardial plague (occurs over a period of years or decades). Within 30 minutes of an occlusion on the first branch of left coronary artery, irreversible myocardial cells damage was occurred. The main change is death (necrosis or apoptosis) of myocardial infarct tissue. Cell therapy perhaps presents new opportunities to enhance cardiac performance through trans- differentiation of the injected stem cells into cardiomyocytes to replace or repair damaged tissues or cells. Experimental data have demonstrated that cell therapy has the potential to repair the damaged myocardium. This expectation and the clinical need for an effective treatment to reduce the injury sustained during an acute MI and to repair the failing heart have accelerated the performance of clinical trials mainly using mesenchymal stem cells (MSC). Platelet-rich fibrin contains several growth factors mainly include platelet derivative growth factor (PDGF–A,B), transforming growth factor(TGF-β), vascular endothelial growth factor (VEGF) and epidermal growth factor(EGF). Platelet growth factors exhibit chemotactic and mitogenic properties that promote and modulate cellular functions involved in tissue healing, cell regeneration and cell proliferation. Platelet-rich fibrin extracts implantation for acute myocardial infarct show optimally in infarct area decrease and new angiogenesis. Fibrosis formation was unclear in myocardium infarct area. Heart function measurement demonstrated improvement of left ventricular ejection fraction (LVEF) and fraction shortening (FS) in platelet-rich fibrin extract groups. The progression of renal disease is characterized by the development of glomerulosclerosis and interstitial fibrosis. Patient with end-stage renal disease have an increased risk of cardiovascular disease. The reduction of nephron mass leads to hypertrophy, hyperfiltration, systemic hypertension and glomerulosclerosis. The advancement of stem cell biology has helped in designing stem cells as a therapeutic tool to accelerate tissue repair. Stem cell therapy is becoming a more viable therapy for chronic kidney injury. Immune modulation and anti-apoptotic effects have been associated with this improvement, suggesting that MSCs can act through glomerulosclerosis mechanisms. We used intra-renal artery autologous MSCs injection to halt fibrosis in a clinic case of feline CKD. We paid attention to clinic renal function recovery after MSCs transplantation. We demonstrated that these cells could halt the process of fibrosis with an improvement in renal function. Mesenchymal stem cells are a leading candidate for cell-based therapies. We introduce artificial acute myocardial infarct model and spontaneous chronic kidney disease cells therapy .In conclusion, a combination therapy of mesenchymal stem cells transplantation plus CoQ10 supplementation or platelet-rich fibrin extract for acute myocardial infarct showed promising results in vivo. Left ventricular function was notably improved with only small areas of fibrosis formation. Clinical results showed the optimal direction that the patient demonstrated blood urea nitrogen and creatinine improvement after intra-renal artery mesenchymal stem cells transfer.

Keywords: Acute myocardial infarction, Chronic glomerulonephritis, Chronic kidney diseases, Ischemic and reperfusion injures, Mesenchymal stem cells, Stem cell therapy, Uremia

並列關鍵字

Acute myocardial infarction ； Chronic glomerulonephritis ； Chronic kidney diseases ； Ischemic and reperfusion injures ； Mesenchymal stem cells ； Stem cell therapy ； Uremia

參考文獻

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