多能性造血幹細胞から血球への初期分化解析

• Project/Area Number: 07269222
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Research Institution: Kansai Medical University
• Principal Investigator: 池原 進 関西医科大学, 医学部, 教授 (90108986)
• Co-Investigator(Kenkyū-buntansha): 比舎 弘子 関西医科大学, 医学部, 助手 (90151422) ; 土岐 純子 関西医科大学, 医学部, 助手 (40077681) ; 長田 憲和 関西医科大学, 医学部, 講師 (40155940) ; 稲葉 宗夫 関西医科大学, 医学部, 講師 (70115947) ; 安水 良知 関西医科大学, 医学部, 講師 (00142753)
• Project Period (FY): 1995
• Project Status: Completed (Fiscal Year 1995)
• Budget Amount: ¥2,500,000 (Direct Cost: ¥2,500,000); Fiscal Year 1995: ¥2,500,000 (Direct Cost: ¥2,500,000)
• Keywords: 骨髄移植 / 造血幹細胞 / ストローマ細胞 / MRL / lprマウス / 主要組織適合抗原

Research Abstract

(1)5-FU処理4日後のマウス骨髄より、Lin^-/CD71^-/ClassI^<high>のpopulationを分離し、この細胞がlong-term reconstituting activity(LTRA)を有すること,すなわち多能性造血幹細胞であることを証明した(PNAS92:5945-5949,1995)。
(2)このようにして分離した多能性造血幹細胞とstromal cellsとの間には、in vivoのみならず、in vitroでも主要組織適合抗原(MHC)の拘束性が存在することを見い出した(Submitted to ﾞBloodﾞ)。
(3)それ故、多能性造血幹細胞がMHCのbarrierを越えて生着するためには、donor側のstromal cellsを補充する必要があることを見い出した(Exp.Hematology23:347-352,1995)。
(4)MRL/lprマウスでは、T細胞を除去した骨髄細胞を移植してもﾞlpr-GVHRﾞが起こるが、MRL/lprマウスのstromal cellsを移植することによって、ﾞlpr-GVHRﾞを抑制し、自己免疫疾患を正常マウスにtransferすることに成功した(J.Immunol 156:79-84,1996)
(5)Lin^-/CD71^-/ClassI^<high>populaionをさらにc-kit^<low>に分別し、Ly5congeneic miceを用いて、LTRAをassayした所、c-kit^-のpopulationがLTRAを有すること,すなわち多能性造血幹細胞は、c-kit^-であることが明らかになった(Submitted to ﾞNatureﾞ)。

Research Products

• [Publications] Hisha H, Nishino T, Kawamura M, and Ikehara S: "Successful bone marrow transplantation by bone grafts in chimeric resistant combination." Exp. Hematol.23. 347-352 (1995)
• [Publications] Adachi Y, Inaba M, Amoh Y, Ikehara S, et al.: "Effect of bone marrow transplantation on anti-phospholipid antibody syndrome in murine lupus mice." Immunobiol.192. 218-230 (1995)
• [Publications] Iwai H, Tomoda K, Inaba M, Ikehara S et al.: "Evidence of cellular supplies to the endolymyphatic sac from systemic circulation." Acta Otolaryngol. (Stockh). 115. 509-511 (1995)
• [Publications] Ogata H, Bradley WG, Ikehara S et al.: "Long-term repopulation of hematolymphoid cells with only a few hemopoietic stem cells in mice." Proc. Natl. Acad. Sci.95. 5945-5949 (1995)
• [Publications] Nishioka N, Toki J, Ikehara S et al.: "Repair mechanism of lupus nephritis in (NZW × NZW) F1 mice by allogeneic bone marrow transplantation" Immunobiology. 192. 279-296 (1995)
• [Publications] Nishino T, Hisha H, Ikehara S et al.: "Hepatocyte growth factor as a hemopoietic regulator." Blood. 85. 3093-3100 (1995)
• [Publications] Kumamoto T, Toki J, Ikehara S et al.: "Cytotoxic effects of irradiation and deoxyguanosine on thymic epithelial cells." Immunobiology. 192. 365-381 (1995)
• [Publications] Inaba M, Inaba K, Ikehara S et al.: "Activation of thymic B cells by signals of CD40 molecules plus interleukin 10." Eur. J. Immunol.25. 1244-1248 (1995)
• [Publications] Haruna H, Inaba M, Ikehara S et al.: "Abnormalities of B cells and dendritic cells in SAMP1 mice" Eur. J. Immunol.25. 1319-1325 (1995)
• [Publications] Lee I, Yu E, Good RA, and Ikehara S: "Presence of eosinophilic precursors in the human thymus: evidence for intra-thymic differentiation of cells in eosinophilic lineage." Pathology International. 45. 655-662 (1995)
• [Publications] Takao F, Yasumizu R, Ikehara S et al.: "Development of insulin-dependent diabetes mellitus in [(NOD + BALB/c)→NOD] mixed allogeneic bone marrow chimeras." Immunobiology. 194. 376-389 (1995)
• [Publications] Fujisawa H, Nishimura T, Inaba M, and Ikehara S: "Suppressive effects of actarit on IgA production in mice: Activation of CD4^+ suppressor T cells in Peyer's patches." Int. J. Immunopharmac. 17. 611-617 (1995)
• [Publications] iyashima S, nagata N, Ikehara S et al.: "Prevention of lpr-graft-versus-host disease and transfer of autoimmune diseases in normal C57BL/6 mice by transplantation of bone marrow cells plus bones (stromal cells) from MRL/lpr mice." J. Immunol.156. 79-84 (1996)
• [Publications] Hosaka N, Nose M, Ikehara S et al.: "Aging of the thymus is a critical factor in successful bone marrow transplantation: Bone marrow transplantation plus fetal thymus grafts as a strategy for treatment of autoimmune diseases in old MRL/+ mice." Proc. Natl. Acad. Sci.(in press).
• [Publications] Ikehara S: "Role of hepatocyte growth factor in hemopoiesis." Leukemia and Lymphoma. (In press).
• [Publications] Good R. A. and Ikehara S: "Preclinical investigations which subserve efforts to employ bone marrow transplantation for rheumatoid or autoimmune diseases." J. Rheumatology. (In press).
• [Publications] Ikehara S, Mizutani H, and Kurata Y: "Autoimmune thrombocytopenic purpura. Critical Reviews in Oncology/Hematology" (Stephen Davis ed.) Elsevier Scientific Publishers Ireland Ltd. Ireland, 33-45 (1995)
• [Publications] Ikehara S: "Bone marrow transplantation as a strategy for the treatment of autoimmune-linked renal diseases. Renal Failure" (William F. Finn eds.) Marcel Dekker, Inc. New York Basel (In press),
• [Publications] Ikehara S: "The prospects for BTM - from mouse to human -. Bone marrow transplantation - Basic and clinical studies -" (Ikehara S, Takaku F, and Good RA, eds.) Springer-Verlag, Inc. Tokyo. Berlin・Heidelberg・New York・London・Paris・Hong Kong Barcelona・Budapest・Singapore (In press),