A higher immune system model by combination of several types of artificial tissues (connective tissue, carcinoma tissue, and lymphoid tissue)

多种人工组织（结缔组织、癌组织、淋巴组织）组合而成的高级免疫系统模型

基本信息

批准号：
13470240
负责人：
KATANO Mitsuo
金额：
$ 10.3万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

This study was focused on the construction of "a higher in vitro immune system model" by combining several types of artificial tissues, including connective tissues, carcinoma tissues, lymphoid tissues, and blood vessel. To perform the research plan, a new research area "tumor technology" was organized by collaboration of "Division of tumor immunology" and "Division of medical technology".Data obtained for duration of this study are as follows:(1) Development of artificial connective tissue: we reconstituted an in vitro connective tissue model which is made up of human fifroblasts and human umbrical vein-derived endothelial cells (HUVEC) in a type-I collagen gel. In this model, HUVEC migrate and form nets of fine blood vessels without addition of any special growth factors.(2) Development of artificial carcinoma tissue: we reconstituted two types of artificial carcinoma tissue. One is a soft tissue type in which we are able to observe microscopically the growth of the two cell types (c … More arcinoma cells and fibroblasts) in real time for more than 30 days. Another is a hard tissue type which is prepared for immunohistochemical analysis. In this model, we can control the growth pattern of carcinoma cells, i.e., expansive or invasive growth, by combination of cytokines used.(3) Development of artificial lymphoid tissue: artificial lymphoid tissue is organized in a type I collagen net supplemented with OKT-3 and fibrinogen, human fibroblasts, lymphocytes, and IL-2. In this model, lymphocytes well proliferate and secrete several types of cytokines such as IFN-g for more than 10 days.(4) Development of preliminary immune system model: we reconstituted a preliminary higher immune system model which is organized in three layers, i.e., dendritic cell layer (lower), carcinoma tissue layer (middle), and lymphoid tissue layer (upper). In this model, we are able to observe microscopically migration of dendritic cells into carcinoma tissue and capture of necrotic carcinoma cells by migrating dendritic cells in real time. We also estimate simply and quickly immunological quality of dendritic cells by measuring IL-12 concentration secreted by dendritic cells.We succeed in developing several types of artificial tissues using various types of cells obtained from surgically resected specimens. However, we did not succeed in connecting these artificial tissues with artificial blood vessel within this research period. Less

这项研究的重点是结合包括连接的组织，癌组织，淋巴组织和血管在内的几种类型的人造组织，将“较高体外免疫系统模型”的构建结合在一起。 To perform the research plan, a new research area "tumor technology" was organized by collaboration of "Division of tumor immunology" and "Division of medical technology".Data obtained for duration of this study are as follows:(1) Development of artificial Connective tissue: we reconstituted an in vitro connected tissue model which is made up of human fifroblasts and human umbrella vein-derived endothelial cells (HUVEC) in a type-I胶原蛋白凝胶。在此模型中，HUVEC在不添加任何特殊生长因素的情况下迁移并形成细血管的网。（2）人造癌组织的发展：我们重构了两种类型的人造癌组织。一种是一种软组织类型，我们能够从显微镜上观察到两种细胞类型（C…更多的弧菌细胞和成纤维细胞）的生长超过30天以上。另一种是用于免疫组织化学分析的硬组织类型。在此模型中，我们可以通过使用的细胞因子的组合来控制癌细胞的生长模式，即膨胀或浸润性生长。（3）人造淋巴组织的发展：人造淋巴组织在I型胶原蛋白网中组织了okt-3和纤维蛋白原，纤维蛋白原，纤维纤维纤维纤维，lymphasts，lymphocytess，lymphopytyt，and-2-2 In this model, lymphocytes well proliferate and secret several types of cytokines such as IFN-g for more than 10 days.(4) Development of preliminary immunosuppression system model: we reconstituted a preliminary higher immunosuppression system model which is organized in three layers, i.e., dendritic cell layer (lower), carcinoma tissue layer (middle), and lymphoid tissue layer (upper).在此模型中，我们能够通过实时迁移树突状细胞来观察将树突细胞迁移到癌组织中并捕获坏死性癌细胞。我们还通过测量由树突细胞分泌的IL-12浓度来简单，快速的树突状细胞的免疫学质量。我们成功地使用了从手术切除的样品获得的各种类型的细胞来开发几种类型的人造时间。但是，在这一研究期间，我们没有成功将这些人造组织与人造血管联系起来。较少的