Hyaluronic Acid/Collagen/Mesenchymal Stem Cells Cardiomyocyte-like Cells Cardiac Patch on the Restoration of Injured Myocardium
Date Issued
2014
Date
2014
Author(s)
Kang, Pei-Leun
Abstract
As well known, cardiomyocytes and neural cells are un-proliferative cells in human. Especially, when the cardiomyocytes damaged, necrotized and loosed its function, the heart is difficult to recover to its original function. To date, in clinical practice, the remedy of this damaged heart is by heart transplantation or heart assist devices. Besides, by implanting regenerative cardiomyocytes into the defect area is now acquiring more attentions from many recent researchers. 5-azacytidine is used to differentiate the mesenchymal stem cells (MSCs) to cardiomyocyte-like cells in these researches. These cardiomyoctye-like cells reveal the spontaneous heart-beat behaviors and with action potentials as normal cardiomyocytes. Type I collagen is the main composition of extracellular matrix. It provides many cellular functions, including providing scaffolds for cells adhesion, migration, differentiation and proliferation. Hyaluronic acid, also possesses biocompatible and biodegradable properties, and used to prepare cell-cultural substrates in tissue engineering applications. The aims (or works) of this study are to prepare 3-D mimetic scaffold (cardiopatch) which be able to provide a natural like micro environment for MSCs growth, to evaluate a chemical stimulant which act as a signal transduction factor, 5-azacytidine is added into the scaffold or medium to stimulate MSCs differentiate to the cardiomyocytes, and to establish animal model with myocardial injury. According to the analysis of water content, porosity and mechanical properties of collagen/hyaluronan composite scaffold, the group composite scaffold (collagen I : HA of 7:1.5) has the maximum elongation. The effect of 5-azacytidine used to induce differentiation of mesenchymal stem cells into cardiomyocyte was positively confirmed by real-time PCR. The results showed that mesenchymal stem cells seeded in composite scaffold expressed higher value of cardiomyocyte specific genes (such as cTnI, β-MHC and α-actin) than the group of cells without using any scaffold but only 5-azacytidine. During the buildup of animal model with myocardial damages, operation was performed to suture the left anterior descending artery and it resulted dark red color change on the distal end of myocardium, biopsy observation also reported that part of myocardium have been replaced with fibroblast with mesenchymal cells alignment or distribution. This proves that by suturing the left anterior descending artery can cause damages to myocardium. The animal study demonstrated that collagen/HA composite scaffolds have the potential for cardiac regeneration applications.
Subjects
間質幹細胞
五氮胞苷
第一型膠原蛋白
透明質酸
心肌梗塞動物模型
心肌修護
Type
thesis
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