应用不同方法体外诱导P19细胞心肌细胞分化的研究
发布时间：2019-02-16 11:27
【摘要】： 一般认为成年哺乳动物的心肌细胞系终末分化细胞,无或仅有有限的再生修复能力,一旦损伤,坏死的心肌只能由无功能的纤维瘢痕组织代替。心肌缺血引发的心肌细胞大量不可逆性缺失、存活的功能性细胞数量下降等多种因素最终将导致心力衰竭的发生,这已成为心血管疾病死亡的主要原因。尽管近些年有研究表明,成体心脏内有可以增殖的心肌干细胞存在,但由于其增殖潜能有限,不足以修复受损的心肌组织。目前,心脏移植成为治疗心肌坏死疾病的一有效途径,但由于供体短缺、复杂的免疫反应及高额的治疗费用限制了其治疗作用。因此,研究者及临床都在寻找新的有效的治疗方案。细胞移植为病损心肌的细胞修复及心功能恢复提供了一种全新的治疗方案。科学家先后应用多种类型的细胞,包括胎儿和新生儿心肌细胞、骨骼肌卫星细胞、平滑肌细胞、成纤维细胞及骨髓来源的细胞进行细胞移植治疗心肌梗塞的动物模型试验,并已取得了较好的进展。但由于细胞来源有限,同时免疫排斥反应等造成移植细胞的大量死亡,因此如何获得大量细胞进行移植以保证足够量的细胞存活或改善移植细胞的存活是目前面临的主要问题。 胚胎畸瘤细胞(embryonal carcinoma cells, EC)细胞与胚胎干细胞(embryonic stem cells, ES)在分化潜能、超微结构、细胞表面抗原和生化特性等方面具有相似性,同时与ES细胞相比,EC细胞在无需饲养层和LIF (leukemia inhibitory factory, LIF)条件下培养即可保持未分化状态,更易于培养,且易于进行基因操作,而且通过分化培养过程EC细胞可从恶性表型转化为非恶性表型,因此EC细胞的研究应用日益受到广大研究者的青睐。P19EC细胞系是McBurney等从C3H/He小鼠畸胎瘤中分离得到的具有多分化潜能的胚胎性干细胞,其在体外培养中单层生长无需饲养层即可迅速大量扩增,经多次传代仍保持胚胎干细胞特有标记,如表面糖蛋白SSEA-1及转录因子Oct-3等。在体外,通过条件培养P19细胞被诱导为包括心肌细胞、骨骼肌细胞、神经元等多种类型的细胞,且分化过程类似
[Abstract]:It is generally believed that adult mammalian myocardial cell line terminal differentiation cells have no or only limited regeneration and repair ability. Once damaged, the necrotic myocardium can only be replaced by nonfunctioning fibrous scar tissue. A large number of irreversible loss of myocardial cells caused by myocardial ischemia and a decrease in the number of viable functional cells will eventually lead to heart failure which has become the main cause of death of cardiovascular disease. Although recent studies have shown that there are proliferative myocardial stem cells in adult hearts, but due to their limited proliferative potential, it is not sufficient to repair damaged myocardial tissue. At present, heart transplantation has become an effective way to treat myocardial necrotic diseases. However, due to the shortage of donors, complex immune response and high treatment costs limit its therapeutic effect. Therefore, researchers and clinical are looking for new and effective treatment. Cell transplantation provides a new therapy for the repair of damaged myocardium and the recovery of cardiac function. Scientists have used a variety of cell types, including fetal and neonatal cardiomyocytes, skeletal muscle satellite cells, smooth muscle cells, fibroblasts and bone marrow-derived cells, to carry out an animal model study of cell transplantation in the treatment of myocardial infarction. Good progress has been made. However, due to the limited source of cells and immune rejection, so how to obtain a large number of cells for transplantation to ensure a sufficient number of cells to survive or improve the survival of transplanted cells is the main problem. The differentiation potential, ultrastructure, cell surface antigen and biochemical characteristics of embryonic teratoma cell (embryonal carcinoma cells, EC) cells were similar to those of embryonic stem cell (embryonic stem cells, ES) cells, and compared with those of ES cells. EC cells could be cultured in undifferentiated condition without feeding layer and LIF (leukemia inhibitory factory, LIF). It was easy to culture and gene manipulation, and EC cells could be transformed from malignant phenotype to non-malignant phenotype through differentiation and culture. Therefore, the research and application of EC cells are increasingly favored by many researchers. P19EC cell lines are embryonic stem cells with multiple differentiation potential obtained from teratoma of C3H/He mice such as McBurney. In vitro culture, monolayer growth can be expanded rapidly without feeding layer, and the specific markers of embryonic stem cells, such as surface glycoprotein SSEA-1 and transcription factor Oct-3, can be maintained after multiple passages. In vitro, P19 cells in conditioned culture were induced to include cardiomyocytes, skeletal muscle cells, neurons and other types of cells. The differentiation process was similar to that of P19 cells.
【学位授予单位】：河北医科大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R329
本文编号：2424398
[Abstract]:It is generally believed that adult mammalian myocardial cell line terminal differentiation cells have no or only limited regeneration and repair ability. Once damaged, the necrotic myocardium can only be replaced by nonfunctioning fibrous scar tissue. A large number of irreversible loss of myocardial cells caused by myocardial ischemia and a decrease in the number of viable functional cells will eventually lead to heart failure which has become the main cause of death of cardiovascular disease. Although recent studies have shown that there are proliferative myocardial stem cells in adult hearts, but due to their limited proliferative potential, it is not sufficient to repair damaged myocardial tissue. At present, heart transplantation has become an effective way to treat myocardial necrotic diseases. However, due to the shortage of donors, complex immune response and high treatment costs limit its therapeutic effect. Therefore, researchers and clinical are looking for new and effective treatment. Cell transplantation provides a new therapy for the repair of damaged myocardium and the recovery of cardiac function. Scientists have used a variety of cell types, including fetal and neonatal cardiomyocytes, skeletal muscle satellite cells, smooth muscle cells, fibroblasts and bone marrow-derived cells, to carry out an animal model study of cell transplantation in the treatment of myocardial infarction. Good progress has been made. However, due to the limited source of cells and immune rejection, so how to obtain a large number of cells for transplantation to ensure a sufficient number of cells to survive or improve the survival of transplanted cells is the main problem. The differentiation potential, ultrastructure, cell surface antigen and biochemical characteristics of embryonic teratoma cell (embryonal carcinoma cells, EC) cells were similar to those of embryonic stem cell (embryonic stem cells, ES) cells, and compared with those of ES cells. EC cells could be cultured in undifferentiated condition without feeding layer and LIF (leukemia inhibitory factory, LIF). It was easy to culture and gene manipulation, and EC cells could be transformed from malignant phenotype to non-malignant phenotype through differentiation and culture. Therefore, the research and application of EC cells are increasingly favored by many researchers. P19EC cell lines are embryonic stem cells with multiple differentiation potential obtained from teratoma of C3H/He mice such as McBurney. In vitro culture, monolayer growth can be expanded rapidly without feeding layer, and the specific markers of embryonic stem cells, such as surface glycoprotein SSEA-1 and transcription factor Oct-3, can be maintained after multiple passages. In vitro, P19 cells in conditioned culture were induced to include cardiomyocytes, skeletal muscle cells, neurons and other types of cells. The differentiation process was similar to that of P19 cells.
【学位授予单位】：河北医科大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R329
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