小鼠牙本质涎磷蛋白基因转染诱导成体间充质干细胞牙向分化的实验研究
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摘要
牙再生的研究属于当前口腔医学领域中的前沿课题。随着现代细胞生物学、分子生物学、材料学技术的进步以及牙齿组织工程概念的发展，使牙齿再生逐步成为可能，引起了越来越多的学者对这一领域的关注。目前牙再生研究中的热点主要集中在对于成牙的种子细胞的选择以及促使种子细胞牙向分化的定向诱导体系。另外，良好的支架材料在组织工程组织的构建中也起着举足轻重的作用。
本课题选取小鼠骨髓间充质干细胞(BM-MSCs)、脂肪基质细胞(ADSCs)这两种成体间充质干细胞为牙再生的候选种子细胞，通过腺病毒介导的基因转染，使以上两种细胞在体外培养过程中高表达小鼠牙本质涎磷蛋白基因，从而模拟成牙本质细胞在体内分化时的内环境，探索了一条通过导入外源性成牙相关基因诱导间充质源性干细胞牙向分化的定向诱导途径。本课题部分阐明了牙齿发育过程中成牙细胞分化时的相关分子机制，通过建立小鼠牙乳头间充质细胞这一成牙前体细胞的自发牙向分化模型作为阳性对照，从基因水平和蛋白水平两个方面论证了过表达牙本质涎磷蛋白的成体间充质干细胞的牙向分化潜能，并从骨髓和脂肪两种组织来源的成体间充质细胞中筛选出适宜应用于牙再生的种子细胞。为了进一步探讨将基因转染诱导后牙向分化的种子细胞应用于构建组织工程化牙髓—牙本质复合体的可行性，我们又自行制备了丝素蛋白与海藻酸钙凝胶
The research of tooth regeneration is a front topic in current stomatology medical domain. Today, tooth regeneration is becoming possible step by step with the modern scientific advancement in cell biology, molecular biology and material science, as well as following the idea of tooth tissue engineering, Meanwhile, more and more scientists show their interest in this field. At present, the research of tooth regeneration is focused on which cell has potential capacity for odontogenesis and how the differentiation of seed cells toward odontogenesis can be induced. In addition, compatible materials for scaffolds play an important role in the construction of tissue engineering organization. As the representative of adult mesenchyma stem cells, we chose bone marrow derived mesenchymal stem cells (BM-MSCs) and adipose tissue derived stromal cells (ADSCs) for our tooth regeneration research. By gene transfection with adenovirus, BM-MSCs and ADSCs were high expressed mouse dentin sialophosphoprotein gene in vitro. We simulated the internal environment of odontablast differentiation in vivo and explored a way to induce mesenchyma stem cells orient differentiation by importing exogenous
本课题选取小鼠骨髓间充质干细胞(BM-MSCs)、脂肪基质细胞(ADSCs)这两种成体间充质干细胞为牙再生的候选种子细胞，通过腺病毒介导的基因转染，使以上两种细胞在体外培养过程中高表达小鼠牙本质涎磷蛋白基因，从而模拟成牙本质细胞在体内分化时的内环境，探索了一条通过导入外源性成牙相关基因诱导间充质源性干细胞牙向分化的定向诱导途径。本课题部分阐明了牙齿发育过程中成牙细胞分化时的相关分子机制，通过建立小鼠牙乳头间充质细胞这一成牙前体细胞的自发牙向分化模型作为阳性对照，从基因水平和蛋白水平两个方面论证了过表达牙本质涎磷蛋白的成体间充质干细胞的牙向分化潜能，并从骨髓和脂肪两种组织来源的成体间充质细胞中筛选出适宜应用于牙再生的种子细胞。为了进一步探讨将基因转染诱导后牙向分化的种子细胞应用于构建组织工程化牙髓—牙本质复合体的可行性，我们又自行制备了丝素蛋白与海藻酸钙凝胶
The research of tooth regeneration is a front topic in current stomatology medical domain. Today, tooth regeneration is becoming possible step by step with the modern scientific advancement in cell biology, molecular biology and material science, as well as following the idea of tooth tissue engineering, Meanwhile, more and more scientists show their interest in this field. At present, the research of tooth regeneration is focused on which cell has potential capacity for odontogenesis and how the differentiation of seed cells toward odontogenesis can be induced. In addition, compatible materials for scaffolds play an important role in the construction of tissue engineering organization. As the representative of adult mesenchyma stem cells, we chose bone marrow derived mesenchymal stem cells (BM-MSCs) and adipose tissue derived stromal cells (ADSCs) for our tooth regeneration research. By gene transfection with adenovirus, BM-MSCs and ADSCs were high expressed mouse dentin sialophosphoprotein gene in vitro. We simulated the internal environment of odontablast differentiation in vivo and explored a way to induce mesenchyma stem cells orient differentiation by importing exogenous
引文
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