Development of 3D culture using cardiac stem cells derived from adult heart and its clinical application

成人心脏心脏干细胞3D培养的开发及其临床应用

• 批准号: 19209047
• 负责人: KAWAGUCHI NANAKO
• 金额: $ 33.11万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-19209047/
• 关键词: 心臓幹細胞c-kit; GATA4; 3次元培養; cardiac; stem cell; 再生医療; 心臓; 培養; characterization; IGF-1; 心筋; 幹細胞; 分化; 再生; 三次元培養; 成体心臓由来幹細胞; 組織幹細胞; 心筋細胞; ナノーテクノロジー; TGF-βスーパーファミリー; 心筋梗塞; c-kit; スキャッフォールド; ティッシュエンジニアリング; 幹 細胞; 遺伝子解析; 成長因子

The aim of this study is to establish 3D culture for transplantation to the infarcted heart. Cardiac stem cells obtained as c-kit positive cells from adult rat hearts were used as a cell source. Even if we use the same method to obtain c-kit positive cells, different genes expression pattern was observed after the long-term culture. Among the various cardiac stem cells (CSCs), GATA4 high-expressing CSCs showed more potential to differentiate into cardiac myocytes than GATA4 low-expressing cells in vitro. Furthermore, these GATA4 high CSCs had more survival effect on the co-cultured cardiacmyocytes derived from adult rat heart than GATA4 low-expressing CSCs. Therefore,GATA4 high CSCs are the appropriate cell source for regenerative medicine for heart failure. We also showed that TGF-βsuperfamily associates with myogenesis.

这项研究的目的是建立3D培养物，以移植到梗塞心脏。从成年大鼠心脏获得的C-KIT阳性细胞获得的心脏干细胞用作细胞来源。即使我们使用相同的方法获得C-kit阳性细胞，在长期培养后也观察到不同的基因表达模式。在各种心脏干细胞（CSC）中，GATA4高表达的CSC显示出比在体外gata4低表达细胞分化为心肌细胞的潜力。此外，这些GATA4高CSC对与GATA4低表达的CSC相比，对源自成年大鼠心脏的共培养心脏细胞的生存作用更大。因此，GATA4高CSC是用于心力衰竭再生医学的合适细胞来源。我们还表明，TGF-βSuperflamily与肌发生相关。

项目成果

c-kit^<pos> GATA-4 high Rat Cardiac Stem Cells Foster Adult Cardiomyocyte Survival Through IGF-1 Paracrine Signaling.

c-kit^<pos> GATA-4 高大鼠心脏干细胞通过 IGF-1 旁分泌信号促进成年心肌细胞存活。

• 发表时间: 2011
• 作者: Kawaguchi N;Smith AJ;Waring CD;Ellison GM.
• 通讯作者: Ellison GM.

Gata4^<high> CSCs foster cardiac myocyte survival through IGF-1 paracrine signaling.

Gata4^<high> CSC 通过 IGF-1 旁分泌信号促进心肌细胞存活。

• 发表时间: 2010
• 期刊: PLoS ONE
• 影响因子: 3.7
• 作者: Kawaguchi N;Smith A;Waring C;Hasan K;Miyamoto S;Matsuoka R;Ellison GM
• 通讯作者: Ellison GM

Gata4^<high> CSCs foster cardiac myocyte survival.

Gata4^<high> CSC 促进心肌细胞存活。

• 期刊: PLoS ONE 5(12)(in press)
• 作者: Kawaguchi N;Smith A;Waring C;Hasan K;Miyamoto S;Matsuoka R;Ellison GM
• 通讯作者: Ellison GM

Characterization of cardiac stem cells derived from adult rat heart.

来自成年大鼠心脏的心脏干细胞的表征。

• 发表时间: 2007
• 作者: 加我君孝;他;佐谷秀行;松村剛毅
• 通讯作者: 松村剛毅

Proteomic analysis of cardiac stem cells derived from adult rat hearts : comparison of the sphere and adherent states of a cardiosphere forming cell clone by protein profiling.

来自成年大鼠心脏的心脏干细胞的蛋白质组学分析：通过蛋白质分析比较心脏球形成细胞克隆的球体和贴壁状态。

• 发表时间: 2008
• 作者: Nanako Kawaguchi;Mitsuyo Machida;Rumiko Matsuoka;Yohtaroh Takagaki
• 通讯作者: Yohtaroh Takagaki