Targeting cancer stem cells in myelodysplastic syndrome

靶向骨髓增生异常综合征中的癌症干细胞

• 批准号: 23591392
• 负责人: TAKENAKA Katsuto
• 金额: $ 3.24万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591392/
• 关键词: 骨髄異形成症候群; がん幹細胞; 免疫不全マウス; 異種移植アッセイ; SIRPA; 幹細胞; 異種移植モデル

Cancer stem cells (CSCs) are therapeutic targets and must be eliminated to cure the patients. However, those cells have not been found yet in myelodysplastic syndrome (MDS). Immunodeficient mice are widely used to reconstitute human hematopoiesis by xenotransplantation of hematopoietic stem cells (HSCs), and this model provides a powerful tool to evaluate biological properties of human cancer stem cells. We found that in xenograft rejection, the innate phagocytic reaction of mouse macrophages could occur because murine SIRPA (mSIRPA) on macrophages cannot bind to human CD47 (hCD47). Thus, introduction of human SIRPA allows mouse macrophage to bind hCD47 on the graft, resulting in inhibition of phagocytic reaction against human cells. Here, we have established a new immunodeficient mouse line, B6-Rag2(null)Il2rg(null) mice with human SIRPA to induce complete macrophage tolerance.This strain should be very useful in xenotransplant experiments to assay MDS stem cells.

癌症干细胞（CSC）是治疗靶标，必须消除才能治愈患者。然而，尚未在骨髓增生异常综合征（MDS）中发现这些细胞。免疫缺陷小鼠被广泛用于通过造血干细胞（HSC）异种移植来重建人类造血功能，该模型为评估人类癌症干细胞的生物学特性提供了有力的工具。我们发现，在异种移植排斥中，由于巨噬细胞上的鼠SIRPA（mSIRPA）不能与人CD47（hCD47）结合，因此可能发生小鼠巨噬细胞的先天吞噬反应。因此，引入人 SIRPA 可使小鼠巨噬细胞与移植物上的 hCD47 结合，从而抑制对人细胞的吞噬反应。在这里，我们建立了一个新的免疫缺陷小鼠系，B6-Rag2(null)Il2rg(null)小鼠，其具有人SIRPA以诱导完全巨噬细胞耐受。该品系在异种移植实验中应该非常有用，以测定MDS干细胞。

项目成果

Quantitation of hematogones at the time of engraftment is a useful prognostic indicator in allogeneic hematopoietic stem cell transplantation

植入时的血红素定量是同种异体造血干细胞移植中有用的预后指标

• 发表时间: 2013
• 期刊: Blood
• 影响因子: 20.3
• 作者: Hayashi K;Nakamura M;Sakamoto W;Yogo T;Miki H;Ozaki S;Abe M;Matsumoto T;Ishimura K.;Shima T,以下16名
• 通讯作者: Shima T,以下16名

Self-Renewing Hematopoietic Stem Cell Is the Primary Target in Pathogenesis of Human Chronic Lymphocytic Leukemia

• DOI: 10.1016/j.ccr.2011.06.029
• 发表时间: 2011-08-16
• 期刊: CANCER CELL
• 影响因子: 50.3
• 作者: Kikushige, Yoshikane;Ishikawa, Fumihiko;Akashi, Koichi
• 通讯作者: Akashi, Koichi

Contribution of bone marrow-derived hematopoietic stem/progenitor cells to the generation of donor-marker⁺ cardiomyocytes in vivo.

• DOI: 10.1371/journal.pone.0062506
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Fukata M;Ishikawa F;Najima Y;Yamauchi T;Saito Y;Takenaka K;Miyawaki K;Shimazu H;Shimoda K;Kanemaru T;Nakamura K;Odashiro K;Nagafuji K;Harada M;Akashi K
• 通讯作者: Akashi K

Stem cell gene expression programs influence clinical outcome in human leukemia

• DOI: 10.1038/nm.2415
• 发表时间: 2011-09-01
• 期刊: NATURE MEDICINE
• 影响因子: 82.9
• 作者: Eppert, Kolja;Takenaka, Katsuto;Dick, John E.
• 通讯作者: Dick, John E.

Quantitation of hematogones at the time of engraftment is a useful prognostic indicator in allogeneic hematopoietic stem cell transplantation.

植入时的血红素定量是同种异体造血干细胞移植中有用的预后指标。

• 发表时间: 2013
• 期刊: Blood
• 影响因子: 20.3
• 作者: Shima T;Miyamoto T;Kikushige Y;Mori Y;Kamezaki K;Takase K;Henzan H;Numata A;Ito Y;Takenaka K;Iwasaki H;Kamimura T;Eto T;Nagafuji K;Teshima T;Kato K;Akashi K.
• 通讯作者: Akashi K.