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Myocardial Regeneration by Cytokine-mobilized Bone Marrow Stem Cells

细胞因子动员的骨髓干细胞的心肌再生

基本信息

批准号：
17591012
负责人：
KAWADA Hiroshi
金额：
$ 2.24万
依托单位：
Tokai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

It has been held for decades that organ systems with regenerative ability are maintained by populations of cells called stem cells which are able to self-renew and generate committed progenies. These stem cells are also believed to be organ/tissue specific. However, this dogma was recently challenged by a number of reports. We first examined myocardial regeneration by cytokine mobilized-bone marrow (BM) cells in mice. We demonstrated that granulocyte colony-stimulating factor (G-CSF) improved cardiac function and survival rate, and BM-derived cells could regenerate infarcted myocardial tissue, differentiating into cardiomyocytes, by using mice whose BM had been replaced with genetically marked BM cells. Since crude BM contain both hematopoietic and non-hematopoietic stem cells, we next assessed the origin of the BM cells which are capable of regenerating cardiomyocytes ; we used clonal studies to determine the origin of BM-derived cardiomyocytes. Our results suggested that the origin of the vast majority of BM-derived cardiomyocytes is mesenchymal stem cells (MSC). However, the number of regenerated cardiomyocytes derived from MSCs was considered to be too small to solely account for the beneficial effect of G-CSF on cardiac remodeling. Then, we focused on the effect of hematopoietic stem cells (HSCs) in the myocardial regeneration. As a result, we found that cardiac myofibroblasts/fibroblasts derive from HSCs and that G-CSF treatment markedly increases the number of HSCs-derived myofibroblasts/fibroblasts in the infarcted area, which reinforced the infarcted ventricular wall, resulting in improved cardiac remodeling, function, and survival. Further, we also demonstrated that monocytes/macrophages could be the precursors of myofibroblasts/ fibroblasts.; MI recruits monocytes which differentiate into myofibroblasts in the infarct region, and administration of G-CSF promotes the recruitment resulting in enhanced cardiac protection.

几十年来，人们一直认为，具有再生能力的器官系统是由一群称为干细胞的细胞维持的，这些干细胞能够自我更新并产生承诺的后代。这些干细胞也被认为是器官/组织特异性的。然而，这一教条最近受到了一些报道的挑战。我们首先研究了细胞因子动员的骨髓(BM)细胞在小鼠中的心肌再生。我们证明，粒细胞集落刺激因子(G-CSF)改善了心功能和存活率，并且BM来源的细胞可以再生梗死的心肌组织，分化为心肌细胞，通过用基因标记的BM细胞取代其BM的小鼠来证明。由于粗制的骨髓含有造血干细胞和非造血干细胞，接下来我们评估了能够再生心肌细胞的骨髓细胞的来源；我们使用克隆研究来确定骨髓来源的心肌细胞的来源。我们的结果提示绝大多数骨髓来源的心肌细胞是间充质干细胞(MSC)。然而，从MSCs来源的再生心肌细胞的数量被认为太少，不能单独解释G-CSF对心脏重塑的有利作用。然后，我们重点研究了造血干细胞在心肌再生中的作用。结果，我们发现心肌成纤维细胞/成纤维细胞来源于HSCs，G-CSF治疗显著增加梗死区HSCs来源的肌成纤维细胞/成纤维细胞的数量，从而加强梗死室壁，从而改善心脏重塑、功能和存活。此外，我们还证明了单核/巨噬细胞可能是肌成纤维细胞/成纤维细胞的前体。MI招募单核细胞，单核细胞在梗死区分化为肌成纤维细胞，而给予G-CSF促进了单核细胞的招募，从而增强了心脏保护。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

サイトカイン投与によって動員した骨髄由来細胞による心筋梗塞後心筋組織再生.

心肌梗死后通过细胞因子动员动员骨髓源性细胞进行心肌组织再生。

DOI：
发表时间：
2005
期刊：
臨床薬理の進歩 26巻
影响因子：
0
作者：
Ishiwata A;et al.;川田浩志
通讯作者：
川田浩志

G-CSF and HGF: Combination of vasculogenesis and angiogenesis synergistically improves recovery in murine hind limb ischemia

DOI：
10.1016/j.yjmcc.2006.11.015
发表时间：
2007-03-01
期刊：
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
影响因子：
5
作者：
Ieda, Yasuyo;Fujita, Jun;Fukuda, Kelichi
通讯作者：
Fukuda, Kelichi

心筋梗塞治療におけるG-CSF-骨髄間葉系幹細胞の動員と分化-.

G-CSF-骨髓间充质干细胞在心肌梗死治疗中的动员和分化-。

DOI：
发表时间：
2006
期刊：
循環器科 60巻
影响因子：
0
作者：
Xin;KQ.;Mizukami;H.;Urabe;M.;Toda;Y.;Shinoda;K.;Yoshida;A.;Oomura;K.;Kojima;Y.;Ichino;M.;Klinman;D.;Ozawa K.;Okuda;K.;菅野仁;川田浩志
通讯作者：
川田浩志

心筋梗塞治療におけるG-CSF -骨髄間葉系幹細胞の動因と文化-.

G-CSF治疗心肌梗塞——骨髓间充质干细胞的激发和培养。