Effect of G-CSF on hematopoietic stem cells derived from aplastic anemia patients in NOD/SCID/γc^<null> mice

G-CSF对NOD/SCID/γc^<null>小鼠再生障碍性贫血患者造血干细胞的影响

• 批准号: 15591103
• 负责人: KOJIMA Seiji
• 金额: $ 2.05万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591103/
• 关键词: NOG mice; JMML; Aplastic Anemia; T cell; 7モノソミー; G-CSF

NOD/SCID/γc^<null>(NOG) mice is a recently developed immunodeficient mouse which lack not only T cell and B cell activity but also NK cell activity. Multilinege differentiation of normal human stem cells is well supported in this mouse model. We tried to transplant to bone marrow cells from patients with juvenile myelomonocytic leukemia(JMML) and aplastic anemia(AA) into NOG mice and produce xenograt model mice.Using this model mice, we demonstrated the engraftment of multilinege human cells in the murine bone marrow and spleen. The FISH method showed the clonal marker in purified CD3^+,CD19^+,and CD56^+ subpopulations. Those findings support the concept that JMML orginates in multilinege hematopoietic stem cells. We also demonstrated the engraftment of human cells in NOG mice transplanted with mononuclear cells derived from patients AA. Different from mice transplanted with stem cells from patients with JMML, most of the engrafted cells belonged to T cell lineage. Mice developed pancytopenia and bone marrow findings are compatible with those of AA. Human cells did not engraft when T cell depleted mononuclear cells were transfused. T cell is indispensable to cause bone marrow failure in this model mice.

NOD/SCID/γc^<null>（NOG）小鼠是近年来发展起来的一种免疫缺陷小鼠，它不仅缺乏T细胞和B细胞活性，而且也缺乏NK细胞活性。正常人干细胞的多系分化在该小鼠模型中得到充分支持。我们尝试将幼年型粒单核细胞白血病（JMML）和再生障碍性贫血（AA）患者的骨髓细胞移植到NOG小鼠体内，并建立了异种鼠模型，利用该模型小鼠，我们证明了多系人细胞在小鼠骨髓和脾脏中的植入。FISH法在纯化的CD 3 ^+、CD 19 ^+和CD 56 ^+亚群中显示克隆标记。这些发现支持JMML起源于多系造血干细胞的概念。我们还证明了人细胞在移植有来自AA患者的单核细胞的NOG小鼠中的植入。与移植JMML患者干细胞的小鼠不同，移植的细胞大部分属于T细胞谱系。小鼠发生全血细胞减少症和骨髓结果与AA一致。当输注T细胞耗尽的单核细胞时，人细胞没有植入。T细胞是导致该模型小鼠骨髓衰竭不可缺少的细胞。

项目成果

小島 勢二: "造血幹細胞移植"医学のあゆみ. 206. 655-659 (2003)

小岛精二：“造血干细胞移植”医学史 206. 655-659 (2003)

Ohga S, Mugishim H, Ohara A, Kojima S, Fujisawa K, Yagi K, Higashigawa M, Tsukimoto I, Aplastic Anemia Committee Japanese Society of Pediatric Hematology: "Diamond-Blackfan anemia in Japan : clinical outcomes of prednisolone therapy and hematopoietic stem

Ohga S、Mugishim H、Ohara A、Kojima S、Fujisawa K、Yagi K、Higashikawa M、Tsukimoto I、日本儿科血液学会再生障碍性贫血委员会：“日本的 Diamond-Blackfan 贫血：泼尼松龙治疗和造血干细胞的临床结果

Diamond-Blackfan Anemia in Japan : Clinical Outcome of Prednisolone Therapyand Hematopoietic Stem Cell Transplantation.

日本的 Diamond-Blackfan 贫血：泼尼松龙治疗和造血干细胞移植的临床结果。

• 发表时间: 2004
• 期刊: Int J Hematol 79
• 作者: Hirano N;Kojima S;et al.
• 通讯作者: et al.

工藤寿子, 小島勢二: "小児白血病診療ハンドブツク Down症候群に発症した白血病"中外医学社. 396 (2003)

工藤久子、小岛诚二：“儿童白血病临床手册：唐氏综合症发展的白血病”中外医学社 396（2003）。

Autoantibodies frequently detected in patients with aplastic anemia

• DOI: 10.1182/blood-2002-11-3409
• 发表时间: 2003-12-15
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Hirano, N;Butler, MO;Nadler, LM
• 通讯作者: Nadler, LM