Clarification of the mechanism of differentiation from hematopoietic stem cell-derived cells to hepatic stellate cells

阐明造血干细胞来源的细胞向肝星状细胞分化的机制

• 批准号: 20591150
• 负责人: MASUYA Masahiro
• 金额: $ 3万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591150/
• 关键词: 単球; 分化; 肝星細胞; MCP-1; CCR2; 肝線維化; 造血細胞; CCR2 antagonist; 四塩化炭素; 骨髄単球系前駆細胞; 肝傷害モデル

We previously clarified that hematopoietic stem cell-derived cells were abele to differentiate into hepatic stellate cells (HpSCs) during carbon tetrachloride (CCl_4)-induced iver injury. Which lineage of cells are true precursors of HpSCs remains unknown. We idoptively transferred neutrophils, monocytes, eosinophils, B cells, or T cells, which were isolated rom enhanced green fluorescent protein (EGFP)-transgenic mice, into CCl_4-injured non-transgenic nice. In the livers of mice given monocytes, EGFP^+ HpSCs were detected. This suggest that a proportion of monocytes are precursors of HpSCs. Monocyte chemoattractant protein-1 (MCP-1) is bought to be associated with the invasion of monocytes into injured liver. CCR2, a receptor for vICP-1, is expressed on monocytes. We examined the effect of CCR2 antagonist against the lifferentiation of monocytes into HpSCs and found that the antagonist suppressed the number of EGFP^+ HpSCs and the area of fibrosis in injured liver.

我们之前阐明了造血干细胞来源的细胞能够在四氯化碳（CCl_4）诱导的肝脏损伤中分化为肝星状细胞（HpSCs）。哪个谱系的细胞是真正的造血干细胞的前体仍然是未知的。我们将从增强绿色荧光蛋白（EGFP）转基因小鼠中分离的中性粒细胞、单核细胞、嗜酸性粒细胞、B细胞或T细胞转移到ccl_4损伤的非转基因小鼠中。在给予单核细胞的小鼠肝脏中，检测到EGFP^+ HpSCs。这表明一部分单核细胞是HpSCs的前体。单核细胞趋化蛋白-1 （MCP-1）被认为与单核细胞侵入损伤的肝脏有关。CCR2是vICP-1的受体，在单核细胞上表达。我们检查了CCR2拮抗剂对单核细胞向HpSCs分化的影响，发现拮抗剂抑制EGFP^+ HpSCs的数量和损伤肝脏的纤维化面积。

项目成果

An efficient method for single hematopoietic stem cell engraftment in mice based on cell-cycle dormancy of hematopoietic stem cells.

• DOI: 10.1016/j.exphem.2010.03.013
• 发表时间: 2010-07
• 期刊: EXPERIMENTAL HEMATOLOGY
• 影响因子: 2.6
• 作者: Abe, Takanori;Masuya, Masahiro;Ogawa, Makio
• 通讯作者: Ogawa, Makio

ADAMTSI3 related markers and von Willebrand factor in plasma from patients with thrombotic microangiopathy (TMA)

血栓性微血管病 (TMA) 患者血浆中的 ADAMTSI3 相关标志物和冯维勒布兰德因子

• 发表时间: 2008
• 期刊: Thromb Res Vol.121, No.6
• 作者: Kobayashi T;Wada H;Nishioka J;Yamamoto M;Matsumoto T;Tamara T;Nomura S;Masuya M;Mori Y;Nakatani K;Nishikawa M;Katayama N;Nobori T
• 通讯作者: Nobori T

Important role for flt3 Ligand in the generation of early B and T cell precursors from human primitive hematopoietic progenitors, revealed by telomerized human stromal cells

端粒化人类基质细胞揭示了 flt3 配体在人类原始造血祖细胞生成早期 B 和 T 细胞前体中的重要作用

• 发表时间: 2010
• 作者: Liu B;Ohishi K;Masuya M;Hamada H;Katayama N
• 通讯作者: Katayama N

Deletion of chromosome arm 15q in acase of minimally differentiatedhypoplastic AML-M0

微分化发育不良AML-M0染色体臂15q缺失

• 发表时间: 2008
• 期刊: Cancer Genet Cytogenet 184(1)
• 作者: Fujieda A;Masuya M;Kitano S,Miyazaki K;Katayama N
• 通讯作者: Katayama N

An efficient method for single hematopoietic stein cell engraftment in mice based on cell-cycle dormancy of hematopoietic stem cells

基于造血干细胞细胞周期休眠的小鼠单造血干细胞移植的有效方法

• 发表时间: 2010
• 期刊: Exp Hematil Vol.38, No.7
• 作者: Abe T;Masuya M;Ogawa M
• 通讯作者: Ogawa M