1991 Fiscal Year Annual Research Report

多能性造血幹細胞の単離・増幅・保存と新しい臨床応用への発展

Research Project

Project/Area Number	01440049
Research Institution	Jichi Medical School
Principal Investigator	三浦恭定自治医科大学, 医学部, 教授 (60048965)
Co-Investigator(Kenkyū-buntansha)	三輪哲義自治医科大学, 医学部, 講師 (40200224) 畠清彦自治医科大学, 医学部, 講師 (80192699) 室井一男自治医科大学, 医学部, 助手 (50190939) 小松則夫自治医科大学, 医学部, 助手 (50186798) 須田年生自治医科大学, 医学部, 助教授 (60118453)
Keywords	造血幹細胞 / 造血因子 / モノクロ-ナル抗体 / CD34 / Cーkit / ムコ多糖 / 脾コロニ- / 抗白血病細胞抗体
Research Abstract	本年度の計画に従い,造血幹細胞の単離をすゝめ,単離した幹細胞が造血因子によりどのように性質を変化させて行くかを検討した。ヒトまたはマウス造血細胞につき次の研究を行う。 1)未熟な造血幹細胞に関連したモノクロ-ナル抗体(CD34,Thy1,SCA1,抗cーkit抗体等)と細胞分離装置を用いて幹細胞の濃縮をすゝめた。この結果マウスではcーkit^+,lineage^-,SCAー1^+の細胞分割に最も未熟な幹細胞があり,それらの2ケに1ケはin vitroでコロニ-をつくり,又,放射線照射マウスの造血を長期間再構築できることがわかった。 2)マウスCD34抗原の遺伝子クロ-ニングを行い,CD34は造血支持細胞側にも発現し幹細胞の培養にも関係している可能性を示した。 3)造血幹細胞を支持する株細胞(PA6,STー2等)と造血細胞の分化を幹細胞因子(SCF)と組合せて使用した幹細胞の自己複製,細胞分裂,増殖を検討した。 4)赤血球の性質を発現している幹細胞の性質を持つ株細胞として巨核球系株細胞UTー7でエリスロポエチンのレセプタ-の発現,および分化に伴う未知の蛋白の出現を検討した。 5)同上の細胞で造血細胞表面のムコ多糖が幹細胞分化に伴って変化し,又,変化したムコ多糖を加えることにより分化をひきおこすことを見出した。 6)新しく入手した抗糖鎖抗休SNH3等が急性骨髄性白血病は認識するが,正常幹細胞とはむすびつかないことを見出した。これを用いて白血病患者等の骨髄から浸潤している腫瘍細胞を除去し自己骨髄移植への応用を具休化するよう検討した。以上これまでの研究は順調に進行した。

Research Products
(12 results)

All Other

All Publications (12 results)

[Publications] Yamaguchi,T.: "Analysis of the survival of mature human eosinophils:Interleukinー5 prevents apoptosis in mature human eosinophils." Blood. 78. 2542-2547 (1991)
[Publications] Honma,Y.: "Induction by some protein kinase inhibitors of differentiation of a mouse megakaryoblastic cell line established by coinfection with abelson murine leukemia virus and recombinant SV40 retrovirus." Cancer Research. 51. 4649-4655 (1991)
[Publications] Ohsaka,A.: "Enhanced neutrophil functions in a patient with colonystimulating activityーproducing Iung cancer." Journal of Internal Medicine. 230. 459-462 (1991)
[Publications] Gunji,Y.: "Support of early Bーcell differentiation in mouse fetal liver by stromal cells and interleukinー7." Blood. 77. 2612-2617 (1991)
[Publications] Tsunoda,J.: "In vivo stem cell function of interleukinー3ーinduced blast cells." Blood. 78. 318-322 (1991)
[Publications] Tanaka,T.: "Stimulatory effects of granulocyte colonyーstimulating factor on Colony ーforming unitsーspleen(CFUーS)differentiation and PreーCFUーS proliferation in mice" Blood. 77. 2597-2602 (1991)
[Publications] Ohara,A.: "Generation of B lymphocytes from a Single hemopoietic progenitor cell in vitro." International Immunology. 3. 703-709 (1991)
[Publications] Nakauchi,H.: "In vitro single cell assay for human stem cells using facs cloneーsorting." Flow cytometry and image analysis for clinical applications. 227-232 (1991)
[Publications] Ema,H.: "Multipotent and committed CD34^+ cells in bone marrow transplantation." Jpn.J.Cancer Res.82. 547-552 (1991)
[Publications] Miura,Y.: "Differentiation pathways of cloneーsorted CD34ーpositive cells." Myelodysplastic Syndrome and Cytokines. 39-48 (1991)
[Publications] Komatsu,.N.: "Establishment and characterization of a human leukemic cell line with megakaryocytic features:Dependency on granulocyteーmacrophage colonyーstimulating factor,interleukin3,or erythropoietin for growth and survival." Cancer Research. 51. 341-348 (1991)
[Publications] Okada,S.: "Effects of interleukin 3,interleukin 6,and granulocyte colonyーstimulating factor on sorted murine splenic progenitor cells." Exp.Hematol.19. 42-46 (1991)

1991 Fiscal Year Annual Research Report

多能性造血幹細胞の単離・増幅・保存と新しい臨床応用への発展

Principal Investigator

三浦 恭定 自治医科大学, 医学部, 教授 (60048965)

Research Products

[Publications] Yamaguchi,T.: "Analysis of the survival of mature human eosinophils:Interleukinー5 prevents apoptosis in mature human eosinophils." Blood. 78. 2542-2547 (1991)

[Publications] Honma,Y.: "Induction by some protein kinase inhibitors of differentiation of a mouse megakaryoblastic cell line established by coinfection with abelson murine leukemia virus and recombinant SV40 retrovirus." Cancer Research. 51. 4649-4655 (1991)

[Publications] Ohsaka,A.: "Enhanced neutrophil functions in a patient with colonystimulating activityーproducing Iung cancer." Journal of Internal Medicine. 230. 459-462 (1991)

[Publications] Gunji,Y.: "Support of early Bーcell differentiation in mouse fetal liver by stromal cells and interleukinー7." Blood. 77. 2612-2617 (1991)

[Publications] Tsunoda,J.: "In vivo stem cell function of interleukinー3ーinduced blast cells." Blood. 78. 318-322 (1991)

[Publications] Tanaka,T.: "Stimulatory effects of granulocyte colonyーstimulating factor on Colony ーforming unitsーspleen(CFUーS)differentiation and PreーCFUーS proliferation in mice" Blood. 77. 2597-2602 (1991)

[Publications] Ohara,A.: "Generation of B lymphocytes from a Single hemopoietic progenitor cell in vitro." International Immunology. 3. 703-709 (1991)

[Publications] Nakauchi,H.: "In vitro single cell assay for human stem cells using facs cloneーsorting." Flow cytometry and image analysis for clinical applications. 227-232 (1991)

[Publications] Ema,H.: "Multipotent and committed CD34^+ cells in bone marrow transplantation." Jpn.J.Cancer Res.82. 547-552 (1991)

[Publications] Miura,Y.: "Differentiation pathways of cloneーsorted CD34ーpositive cells." Myelodysplastic Syndrome and Cytokines. 39-48 (1991)

[Publications] Komatsu,.N.: "Establishment and characterization of a human leukemic cell line with megakaryocytic features:Dependency on granulocyteーmacrophage colonyーstimulating factor,interleukin3,or erythropoietin for growth and survival." Cancer Research. 51. 341-348 (1991)

[Publications] Okada,S.: "Effects of interleukin 3,interleukin 6,and granulocyte colonyーstimulating factor on sorted murine splenic progenitor cells." Exp.Hematol.19. 42-46 (1991)

三浦恭定自治医科大学, 医学部, 教授 (60048965)