Successful allogeneic bone marrow transplantation by injection of bone marrow stromal cells and the cytological and molecular-biological analyses of their role

通过注射骨髓基质细胞成功进行同种异体骨髓移植及其作用的细胞学和分子生物学分析

基本信息

  • 批准号:
    11670229
  • 负责人:
  • 金额:
    $ 0.58万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    1999
  • 资助国家:
    日本
  • 起止时间:
    1999 至 2000
  • 项目状态:
    已结题

项目摘要

We have previously found that bone marrow transplantation (BMT) can be used to treat autoimmune diseases and that successful BMT can be achieved by BMT plus bone grafts even if in chimerism-resistant combinations such as [normal→ MRL/1pr] and [DAB/2→C57BL/6] (J.Immunol.152 : 3991, 1994 & Exp.Hematol.23 : 347, 1995). Bone marrow stromal cells (BMSCs) of the recipients are replaced partially by donor-type BMSCs, indicating that donor-derived BMSCs migrate from the engrafted bones to the recipient bones and offer a suitable environment for donor hemopoietic stem cells (HSCs). I have investigated the role of BMSCs as BMT-facilitating cells and obtained the following results.1.After BMT plus bone grafts, donor-derived BMSCs can migrate into recipient thymus and participate there in positive selection (Exp. Hematol. 28 : 950, 2000).2.When recipient mice were injected HSCs along with donor BMSCs obtained after 3-4 week-culture, by portal vein (PV) route, hemopoietic colony fomation was markedly increased in the recipient spleen and finally higher survival rate could be achieved (but not intravenous (IV) route). Hematopoietic colonies composed of both donor hemopoietic cells and BMSCs do exist in the liver of these mice. These findings suggest trapped BMSCs and HSCs do form hemopoietic colonies in the liver and then migrate into recipient bone marrow and spleen to form CFU-S (Stem Cells 19 : 144, 2001).3.BMT of bone marrow cells by PV route, followed by additional administration of bone marrow cells by IV route, leads a successful reconstitution even if in chimerism-resistant combinations (Stem Cells in press).4.MHC class Ia (H-2 K and D loci) determines the restriction between HSCs and BMSCs (Stem Cells 19 : 46, 2001).
我们以前已经发现骨髓移植(BMT)可用于治疗自身免疫性疾病,并且即使在嵌合体抗性组合如[正常→ MRL/1 pr]和[DAB/2→ C57 BL/6]中,通过BMT加骨移植物也可实现成功的BMT(J.Immunol.152:3991,1994和Exp.Hematol.23:347,1995)。受者的骨髓基质细胞(BMSCs)部分被供体型BMSCs替代,表明供体来源的BMSCs从移植骨迁移到受者骨,并为供体造血干细胞(HSCs)提供合适的环境。本课题研究了骨髓间充质干细胞作为骨髓移植促进细胞的作用,获得以下结果:1.骨髓移植加骨移植后,供体来源的骨髓间充质干细胞可迁移到受体胸腺,并参与胸腺的正向选择(Exp.血液二十八:2.将培养3-4周的供体骨髓间充质干细胞与造血干细胞沿着经门静脉途径注射给受鼠,受鼠脾内造血集落形成明显增加,最终获得较高的存活率(但静脉途径不能)。在这些小鼠的肝脏中确实存在由供体造血细胞和BMSCs组成的造血集落。这些结果表明,捕获的BMSCs和HSC确实在肝脏中形成造血集落,然后迁移到受体骨髓和脾脏中形成CFU-S(干细胞19:144,2001)。3.通过PV途径进行骨髓细胞的BMT,然后通过IV途径另外施用骨髓细胞,即使在嵌合体抗性组合中,(Stem Cells in press).4.MHCClass Ia(H-2K和D基因座)决定HSC和BMSC之间的限制(Stem Cells 19:46,2001)。

项目成果

期刊论文数量(18)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Kushida T,Inaba M,Hisha H,…Ikehara S: "Crucial role of donor-derived stromal cells in successful treatment for intractable autoimmune diseases in MRL/lpr mice by BMT via portal vein"Stem Cells. (In press).
Kushida T、Inaba M、Hisha H、…Ikehara S:“供体来源的基质细胞在通过门静脉 BMT 成功治疗 MRL/lpr 小鼠难治性自身免疫性疾病中的关键作用”干细胞(正在出版)。
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    0
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Li Y,Hisha H,Inaba M,Lian Z,Yu C,Kawamura M,-Ikehara S: "Evidence for migration of donor bone marrow stromal cells into recipient thymus after bone marrow transplantation plus bone grafts ; a role of stromal cells in positive selection."Exp.Hematol.. 28.
Li Y,Hisha H,Inaba M,Lian Z,Yu C,Kawamura M,-Ikehara S:“骨髓移植加骨移植后供体骨髓基质细胞迁移到受体胸腺的证据;基质细胞在阳性中的作用
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    0
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  • 通讯作者:
Iguchi T, Sogo S, Hisha H, Taketani S, Adachi Y, Miyazaki R, Ogata H, Masuda S, Sasaki R, Ito M, Fukuhara S & Ikehara S: "HGF activates signal transduction from EPO receptor on human cord blood CD34^+/CD45^+ cells."Stem Cells. 17. 82-91 (1999)
井口 T、Sogo S、Hisha H、竹谷 S、安达 Y、宫崎 R、绪方 H、增田 S、佐佐木 R、伊藤 M、福原 S
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    0
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HISHA Hiroko其他文献

HISHA Hiroko的其他文献

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{{ truncateString('HISHA Hiroko', 18)}}的其他基金

Examination of neuroregulation in intestinal epithelium using stem cell differentiation-visualizing mice
使用干细胞分化可视化小鼠检查肠上皮的神经调节
  • 批准号:
    23590953
  • 财政年份:
    2011
  • 资助金额:
    $ 0.58万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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骨髓基质细胞的胞吞作用和骨老化
  • 批准号:
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    2022
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Efferocytosis by Bone Marrow Stromal Cells and Bone Aging
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PECAM-1与骨髓基质细胞对白血病细胞相互作用的分析
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CD 271骨髓基质细胞治疗退行性软骨的基础研究
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佛波醇12
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GATA2在骨髓基质细胞中的作用
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使用源自骨髓基质细胞的工程外泌体开发多发性骨髓瘤的新疗法
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