Co-Investigator(Kenkyū-buntansha) |
UCHIYAMA Akihiko Kyushu University, Faculty of Medicine University Hospital, Ass., 医学部附属病院, 助手 (20294936)
MORISAKI Takashi Kyushu University, Graduate School of Medical Sciences, Ass., 大学院・医学研究院, 助手 (90291517)
SUEISHI Katsuo Kyushu University, Graduate School of Medical Sciences, Prof., 大学院・医学研究院, 教授 (70108710)
MATSUDA Takehisa Kyushu University, Graduate School of Medical Sciences, Prof., 大学院・医学研究院, 教授 (60142189)
TANAKA Masao Kyushu University, Graduate School of Medical Sciences, Prof., 大学院・医学研究院, 教授 (30163570)
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Research Abstract |
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
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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
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