骨髓間質幹細胞併用血小板纖維蛋白釋放液治療I型糖尿病小鼠

Abstract

糖尿病 (Diabetes Mellitus, DM) 是一種由於體內缺乏胰島素或是胰島素在靶細胞不能發揮正常的生理作用而起的糖、蛋白質和脂肪代謝紊亂，表現為高血糖的一種綜合性的慢性代謝性病症。是由遺傳因素和環境因素相互作用所引起的常見病，高血糖為其主要的臨床標誌，常見症狀主要有多飲、多尿、多食以及消瘦等。其分為I型糖尿病與 II型糖尿病。I型糖尿病是一種慢性疾病，其特徵為自身免疫系統破壞分泌胰島素的胰腺β細胞，結果導致自身無法產生足夠的胰島素，並引起空腹和餐後高血糖。典型症狀是多尿，煩渴，並多食。 幹細胞 (Stem Cell, SC) 是一類具有自我複製能力和分化能力的未分化或分化程度較低的細胞。一部分幹細胞位於成體組織，如間質幹細胞 (Mesenchymal Stem Cells, MSCs)，其為一種多能幹細胞，可分化為心肌細胞、軟骨細胞、脂肪細胞等間質幹細胞在不同條件下可分化為多種細胞，為臨床上的應用提供了很大的可能性。 血小板，除具有凝集作用外，還含有許多與細胞增殖有關的因子存在。在組織修復和再生過程中，可調節體內新陳代謝，並促進組織的修復和癒合。富血小板纖維蛋白 (Platelet-rich Fibrin, PRF) 的製作過程簡便，無添加，條件溫和。纖維蛋白的聚合過程是緩慢而自然的凝結過程，與正常的纖維蛋白網的聚合過程類似，這種結構可以導致引導細胞遷移、增殖和癒合能力的增強，並且可以網羅住更多的血小板，讓血小板生長因子緩慢釋放，延長作用的時間。 本文利用間質幹細胞配合PRF的釋放液通過靜脈注射治療I型糖尿病小鼠，以及間質幹細胞在體外定向誘導分化成為類胰島細胞分泌團塊進行治療，並對其結果進行評估與比較。通過對血糖結果與組織學的評估得到結論，通過靜脈注射幹細胞、PRF釋放液、分化後的細胞都能對胰臟起到修復的作用，治療效果為分化後的細胞與間質幹細胞配合PRF釋放液相當，且最好，單獨使用間質幹細胞效果其次，單獨使用PRF釋放液效果最差。

Diabetes Mellitus is a serious disease in which the body cannot properly control the amount of sugar in your blood because it does not have enough insulin. And it can be divided into Type I diabetes and Type II diabetes. Type I diabetes mellitus is a chronic disease characterized by the autoimmune destruction of insulin-secreting pancreatic beta-cells, which results from the body's failure to produce enough insulin and gives rise to fasting and postprandial hyperglycemia. The classic symptoms are polyuria (excessive urination), polydipsia (excessive thirst), and polyphagia (excessive hunger). Stem Cells are an unspecialized cell that gives rise to differentiated cells. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells which can differentiate into cardiac cells, chondrocytes, adipocytes and so on. And mesenchymal stem cells can differentiate into differentiate into specific cells under different conditions. Platelet-rich fibrin (PRF) is a source of autogenic neotype biomaterial, which is rich in cytokine and growth factors, and is called new generation of platelet concentrates. The molecular constitution of PRF is similar to nature blood clot, and to provide location with migration, proliferation, and differentiation for rhagiocrine cell. Currently, the slow polymerization during PRF preparation seems to generate a fibrin network very similar to the natural one. Such a network leads to a more efficient cell migration and proliferation and thus cicatrization. In our research, the mesenchymal stem cells derived from mouse bone marrow and adipose can be induced to proliferate and differentiate into islet-like cell clusters and to form islet-like structure. The stem cell differentiated islet could ameliorate the glyco metabolic disorder in diabetic animals and the result is as good as the group which use mesenchymal stem cells with PRF releasate.