人脐带间充质干细胞在PHBVHHx生物材料支架上分化为肝细胞的研究
发布时间：2019-01-27 21:57
【摘要】：肝脏作为机体最重要的生命器官之一,在机体的代谢、排毒、循环调节等方面发挥着重要的功能,同时肝脏疾病也是影响人体健康的重要疾病之一,目前,对于一些严重的末期肝脏疾病,诸如肝癌,急性肝衰竭等,最为有效的治疗手段就是原位肝移植,然而由于供体肝缺乏,高昂的费用,以及异种免疫排斥等原因,使其临床应用受到很大的限制。因此,一种新的以细胞为基础的肝病治疗法,例如肝组织工程,旨在造出一个人造肝组织使其成为患者肝组织的替代品。肝脏组织工程为肝病的治疗带来了新的希望。 近年来间充质干细胞的研究和应用备受关注,间充质干细胞(mesenchymal stem cells, MSCs)具有很强增殖能力和多分化潜能,具有跨胚层分化能力,而且间充质干细胞容易获得,易于分离培养和扩增。因此间充质干细胞(MSCs)作为组织工程的种子细胞具有良好的应用前景。在本论文中间充质干细胞分离自人脐带沃顿胶质组织(Wharton’s jelly)经过体外诱导培养分化为肝样细胞,并将其与骨髓来源的间充质干细胞(BM-MSCs)进行比较。研究表明脐带间充质干细胞和骨髓间充质干细胞都具有相似的间充质干细胞特性,都能在体外诱导分化为成骨细胞,脂肪细胞和软骨细胞。经过肝细胞诱导分化液的诱导培养后,分化后的细胞都能够表达肝细胞特异性的蛋白和基因(albumin, AFP, CK-18)并且具有糖原合成能力和低密度脂蛋白吸收能力,结果表明脐带间充质干细胞和骨髓间充质干细胞具有相似的肝细胞分化潜能。但是与骨髓间充质干细胞相比,脐带间充质干细胞更容易获得,具有低的免疫原性,所以脐带间充质干细胞作为组织工程的种子细胞更具优势。聚羟基脂肪酸酯(PHA)是微生物在营养不平衡的环境下产生的一类高分子生物线性聚酯,研究表明PHA有良好的生物相容性及生物可降解性,三聚物PHBVHHx与其他的PHA材料相比具有更好的生物相容性,更利于细胞的贴附生长,所以PHBVHHx在肝组织工程的研究上具有很好的应用前景。 本研究中我们选择脐带间充质干细胞作为肝组织工程的种子细胞,三聚物PHBVHHx作为支架材料,研究生物材料PHBVHHx支架对脐带间充质干细胞体外分化为肝细胞的影响。本实验研究结果表明PHBVHHx支架能够支持脐带间充质干细胞的生长,并且脐带间充质干细胞在PHBVHHx支架上在肝细胞诱导液的诱导培养下能够分化肝样细胞。总之本研究可以为肝组织工程的研究提供一定的实验信息和数据。
[Abstract]:As one of the most important living organs of the body, liver plays an important role in metabolism, detoxification, circulatory regulation and so on. At the same time, liver disease is also one of the important diseases affecting human health. For some serious end-stage liver diseases, such as liver cancer and acute liver failure, the most effective treatment is orthotopic liver transplantation. However, due to lack of donor liver, high cost, and xenoimmune rejection, etc. Its clinical application is restricted greatly. Therefore, a new cell-based treatment for liver diseases, such as liver tissue engineering, aims to create an artificial liver tissue as a substitute for patient liver tissue. Liver tissue engineering offers new hope for the treatment of liver disease. In recent years, the research and application of mesenchymal stem cells (MSCs) have attracted much attention. Mesenchymal stem cells (mesenchymal stem cells, MSCs) have strong proliferative ability, multi-differentiation potential, transdermal differentiation ability and easy to obtain mesenchymal stem cells. It is easy to isolate, culture and amplify. Therefore, mesenchymal stem cell (MSCs) as seed cells of tissue engineering has a good application prospect. Mesenchymal stem cells (MSCs) isolated from human umbilical cord Wharton glial tissue (Wharton's jelly) were induced to differentiate into hepatoid cells in vitro and were compared with bone marrow-derived mesenchymal stem cells (BM-MSCs). The results showed that both umbilical cord mesenchymal stem cells and bone marrow mesenchymal stem cells had similar characteristics of mesenchymal stem cells and could be induced to differentiate into osteoblasts, adipocytes and chondrocytes in vitro. The differentiated cells were able to express hepatocyte specific protein and gene (albumin, AFP, CK-18) and had the ability of glycogen synthesis and low density lipoprotein absorption. The results showed that cord mesenchymal stem cells and bone marrow mesenchymal stem cells had similar hepatocyte differentiation potential. However, compared with bone marrow mesenchymal stem cells, umbilical cord mesenchymal stem cells are easier to obtain and have low immunogenicity, so umbilical cord mesenchymal stem cells have more advantages as seed cells for tissue engineering. Polyhydroxyfatty acid ester (PHA) is a kind of macromolecule linear polyester produced by microorganisms in the environment of unbalanced nutrition. The research shows that PHA has good biocompatibility and biodegradability. Compared with other PHA materials, trimer PHBVHHx has better biocompatibility and more favorable for cell adhesion growth, so PHBVHHx has a good application prospect in liver tissue engineering. In this study we chose umbilical cord mesenchymal stem cells as seed cells of liver tissue engineering and trimer PHBVHHx as scaffold materials to study the effect of PHBVHHx scaffold on the differentiation of umbilical cord mesenchymal stem cells into hepatocytes in vitro. The results showed that PHBVHHx scaffold could support the growth of umbilical cord mesenchymal stem cells and that umbilical cord mesenchymal stem cells could differentiate into hepatoid cells induced by hepatocyte inducer on PHBVHHx scaffold. In a word, this study can provide some experimental information and data for liver tissue engineering.
【学位授予单位】：汕头大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R329
本文编号：2416736
[Abstract]:As one of the most important living organs of the body, liver plays an important role in metabolism, detoxification, circulatory regulation and so on. At the same time, liver disease is also one of the important diseases affecting human health. For some serious end-stage liver diseases, such as liver cancer and acute liver failure, the most effective treatment is orthotopic liver transplantation. However, due to lack of donor liver, high cost, and xenoimmune rejection, etc. Its clinical application is restricted greatly. Therefore, a new cell-based treatment for liver diseases, such as liver tissue engineering, aims to create an artificial liver tissue as a substitute for patient liver tissue. Liver tissue engineering offers new hope for the treatment of liver disease. In recent years, the research and application of mesenchymal stem cells (MSCs) have attracted much attention. Mesenchymal stem cells (mesenchymal stem cells, MSCs) have strong proliferative ability, multi-differentiation potential, transdermal differentiation ability and easy to obtain mesenchymal stem cells. It is easy to isolate, culture and amplify. Therefore, mesenchymal stem cell (MSCs) as seed cells of tissue engineering has a good application prospect. Mesenchymal stem cells (MSCs) isolated from human umbilical cord Wharton glial tissue (Wharton's jelly) were induced to differentiate into hepatoid cells in vitro and were compared with bone marrow-derived mesenchymal stem cells (BM-MSCs). The results showed that both umbilical cord mesenchymal stem cells and bone marrow mesenchymal stem cells had similar characteristics of mesenchymal stem cells and could be induced to differentiate into osteoblasts, adipocytes and chondrocytes in vitro. The differentiated cells were able to express hepatocyte specific protein and gene (albumin, AFP, CK-18) and had the ability of glycogen synthesis and low density lipoprotein absorption. The results showed that cord mesenchymal stem cells and bone marrow mesenchymal stem cells had similar hepatocyte differentiation potential. However, compared with bone marrow mesenchymal stem cells, umbilical cord mesenchymal stem cells are easier to obtain and have low immunogenicity, so umbilical cord mesenchymal stem cells have more advantages as seed cells for tissue engineering. Polyhydroxyfatty acid ester (PHA) is a kind of macromolecule linear polyester produced by microorganisms in the environment of unbalanced nutrition. The research shows that PHA has good biocompatibility and biodegradability. Compared with other PHA materials, trimer PHBVHHx has better biocompatibility and more favorable for cell adhesion growth, so PHBVHHx has a good application prospect in liver tissue engineering. In this study we chose umbilical cord mesenchymal stem cells as seed cells of liver tissue engineering and trimer PHBVHHx as scaffold materials to study the effect of PHBVHHx scaffold on the differentiation of umbilical cord mesenchymal stem cells into hepatocytes in vitro. The results showed that PHBVHHx scaffold could support the growth of umbilical cord mesenchymal stem cells and that umbilical cord mesenchymal stem cells could differentiate into hepatoid cells induced by hepatocyte inducer on PHBVHHx scaffold. In a word, this study can provide some experimental information and data for liver tissue engineering.
【学位授予单位】：汕头大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R329
【参考文献】
相关期刊论文 前1条
1 ;Human umbilical cord Wharton's Jelly-derived mesenchymal stem cells differentiation into nerve-like cells[J];Chinese Medical Journal;2005年23期
，本文编号：2416736
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