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“通过结合人造组织的严重程度类型的IVE组织，癌组织，淋巴组织和血管。为了执行研究计划，通过协作进行了新的研究区域肿瘤技术”来组织。医疗技术的划分”。为这项研究提供的DATA如下：（1）人工连接组织的发展：我们重建了由人类肥大的肥大和humbril静脉衍生细胞细胞（HUVEC）组成的体外连接组织模型（HUVEC）在I型胶原蛋白凝胶中。（C更多的动脉瘤细胞和成纤维细胞）实时使用30天以上。在I型胶原蛋白网络中，用OKT-3 TES和IL-2在此模型中，淋巴细胞，增殖和分泌严重性的细胞因子（例如IFN-G）超过10天。层（较低），癌组织层（中）和淋巴组织层（上），我们将通过实时估计，树突状细胞迁移到坏死MA细胞的癌中通过测量IL -12浓度的细胞的模拟和免疫学质量。我们成功地开发了通过手术切除标本的人工组织类型的严重性类型。较少的