Development of new cardiovascular regeneration therapy by regulating apoptosis and bone marrow stem cell mobilization

通过调节细胞凋亡和骨髓干细胞动员开发新的心血管再生疗法

• 批准号: 16590667
• 负责人: TAKAHASHI Masafumi
• 金额: $ 2.24万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590667/
• 关键词: cytokine; atherosclerosis; myocardial infarction; myocarditis; regeneration; bone marrow; angiogenesis; 骨髄幹細胞; 血管内皮前駆細胞; 血管平滑筋細胞; マウス; アポトーシス; 心筋細胞

We have previously reported the effectiveness and safety of therapeutic angiogenesis by transplantation of autologous bone marrow cells to ischemic limbs ; however, this therapy needs general anesthesia to obtain bone marrow cells. To develop more efficient therapy using bone marrow cells, we examined the effect of several factors, such as G-CSF, M-CSF, and erythropoietin (EPO), that regulate apoptosis and bone marrow cell mobilization in rat and murine models of cardiovascular diseases. The major findings of this study are : (1) G-CSF mobilized endothelial progenitor cells, accelerated reendothelialization, and decreased neointimal formation after vascular injury ; (2) M-CSF induced neointimal formation in the early stages after vascular injury through activation of SDF-1/CXCR4 system ; (3) EPO attenuated inflammatory cell infiltration and cytokine expression, and it improved cardiac function and reduced cardiac inflammation in autoimmune myocarditis. These findings suggest the therapeutic potential of these factors in cardiovascular diseases.

我们以前曾报道过自体骨髓细胞移植到缺血肢体的治疗性血管生成的有效性和安全性，然而，这种治疗需要全身麻醉才能获得骨髓细胞。为了开发使用骨髓细胞的更有效的治疗，我们研究了几种因素，如G-CSF，M-CSF和促红细胞生成素（EPO），调节细胞凋亡和骨髓细胞动员在大鼠和小鼠模型的心血管疾病的影响。本研究的主要结果是：（1）G-CSF动员内皮祖细胞，促进血管损伤后再内皮化，减少新生内膜形成：（2）M-CSF通过激活SDF-1/CXCR 4系统，在血管损伤后早期诱导新生内膜形成;（3）EPO可减轻心肌炎性细胞浸润和细胞因子表达，改善心功能，减轻心肌炎症反应。这些发现表明这些因素在心血管疾病中的治疗潜力。

项目成果

Changes in cardiac lipid metabolism during sepsis: The essential role of very low-density lipoprotein receptors

• DOI: 10.1016/j.cardiores.2005.11.014
• 发表时间: 2006-02-01
• 期刊: CARDIOVASCULAR RESEARCH
• 影响因子: 10.8
• 作者: Jia, LJ;Takahashi, M;Ikeda, U
• 通讯作者: Ikeda, U

Erythropoietin attenuates the development of experimental autoimmune myocarditis.

促红细胞生成素可减轻实验性自身免疫性心肌炎的发展。

• 发表时间: 2007
• 期刊: Cardiovasc Drug Ther 21
• 作者: Hirose S;Takahashi M;Ogawa R;Morimoto H;Izawa A;Sato H;Ise H;Hongo M;Ikeda U
• 通讯作者: Ikeda U

Efficacy of mycophenolic acid combined with a novel immunomodulator KRP-203 in rat heart transplantation models.

霉酚酸联合新型免疫调节剂 KRP-203 在大鼠心脏移植模型中的疗效。

• 发表时间: 2006
• 期刊: J Heart Lung Transpl 25
• 作者: Suzuki C;Takahashi M;Morimoto H;Izawa A;Ise H;Fujishiro J;Murakami T;Ishiyama J;Nakada A;Nakayama J;Ikeda U;Kobayashi E.
• 通讯作者: Kobayashi E.

M-CSF accelerates neointimal formation in the early phase after vascular injury in mice the critical role of the SDF-1-CXCR4 system

• DOI: 10.1161/01.atv.0000250606.70669.14
• 发表时间: 2007-02-01
• 期刊: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
• 影响因子: 8.7
• 作者: Shiba, Yuji;Takahashi, Masafumi;Ikeda, Uichi
• 通讯作者: Ikeda, Uichi

G-CSF accelerates reendothelialization and reduces neointimal formation after vascular injury in mice.

G-CSF 可加速小鼠血管损伤后的再内皮化并减少新内膜形成。

• 发表时间: 2006
• 期刊: Cardiovasc Res 70
• 作者: Yoshioka T;Takahashi M;Shiba Y;Suzuki C;Morimoto H;Izawa A;Ise H;Ikeda U
• 通讯作者: Ikeda U