細胞工学の進歩とその医学への応用
スポンサーリンク
概要
- 論文の詳細を見る
The characteristics of the medical science is always fresh utilizing and applying newest techniques developed in the surrounding scientific fields at each time. The molecular biology developed after the 2nd world war has given so great impacts that some technological problems in the medical science have been broken through and many excellent new findings in molecular level have been taken. The most important technique is the culture of somatic cells from human body and the cell biology in vitro was followed by the development of a lot of cell engineering techniques which was quite effective to the research for medical science. Cell fusion is one of the cell engineering techniques. I would like to talk about the 3 kinds of results which have been open corresponding to the cell fusion. I. Gene complementation test became possible among families of a hereditary disease by this technique which was the daybreak of the genetic analyses of human hereditary diseases in laboratories. For a example, 10 complementation groups have been detected in xeroderma pigmentosum which is a ressesive hereditary disease showing deficiency in excision repair of damaged DNA. The next step is the isolation of the gene relating to each complementation group. Recently, a gene corresponding to the complementation group A has been isolated in my lab. II. As well known, formation of hybridomas producing monoclonal antibodies has given a great impact to cell biology, diagnosis of some diseases and the treatment of cancers. Immunotoxin (a hybrid of molecules of a monoclonal antibody able to identify cancer cell surface alone and a toxin such as fragment A of diphtheria toxin or ricin toxin) has also been expected for the cancer treatment. III. Finally, I would like to show the selective killing of cells having the capacity of cell fusion by the infection of viruses. Analysis of cell fusion mechanism by HVJ (Sendai virus) suggested that the cell-to-cell fusion is carried out at the sites of the two cell membranes containing no intramembrane particles. The cell membrane area exposing naked lipid bilayer is induced by the interaction of HVJ envelopes with cell membranes at 37℃. The naked lipid bilayer seems to fuse also with simple liposomes added. In the case of native cell membranes without the appearance of naked lipid bilayer, no fusion occurs with simple liposomes but they can only fuse effectively if the liposomes contain viral spike proteins (F and HANA) on their surface. This finding has been utilized successfully for the selective killing of SSPE (Subacute Screrosing Pan-Encephalitis) virus infected cells, using simple liposomes containing fragment A of diphtheria toxin. SSPE virus is a mutant of measles virus defective in its maturation step. The spreading of the infected region depends on introduction of the viral genome through fusion of the infected cells with native cells. Thus, the infective source of SSPE could be removed but when the infected cells are killed totally. When SSPE virus infected cells were put on a monolayer of normal HEL (human embryonic lung) cells, many syncytium appeared by fusion of the two kinds of cells then they degenerated and many plaques were produced. On further incubation, normal HEL cells were totally infected by SSPE virus and no cell remained on the plate. Under the conditions, when liposomes containing toxin were exposed to a cell mixture of normal HEL cells and SSPE virus infected HEL cells, the latter cells were killed selectively by the toxin and the vacant areas of plaques were recovered by the growth of non-infected HEL cells remaining, then finally, the plate became covered by a newly produced monolayer of normal HEL cells. The above findings encourage us to treat SSPE patient by this kind of liposomes. Some experiments using hamsters in our group shown on effectiveness of this treatment in vivo.
- 社団法人日本産科婦人科学会の論文
- 1988-08-01