ESTABLISHMENT OF THE HEART FAILURE THERAPY USING REGENERATED CARDIOMYOCYTE FROM BONE MARROW

建立利用骨髓再生心肌细胞治疗心力衰竭的方法

• 批准号: 12307016
• 负责人: OGAWA Satoshi
• 金额: $ 27.84万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12307016/
• 关键词: STEM CELL; REGENERATION; BONE MARROW; CARDIOMYOCYTE; TRANSDIFFERENTIATION; HEART FAILURE; TRANSPLANTATION; 再生医学; 骨髄細胞; 発生

WE HAVE ISOLATED A CARDIOMYOGENIC CELL LINE (CMG CELL) FROM MURINE BONE MARROW MESENCHYMAL STEM CELLS. THE CELLS SHOWED A FIBROBLAST-LIKE MORPHOLOGY, BUT THE MORPHOLOGY CHANGED AFTER 5-AZACYTIDINE EXPOSURE. THEY BEGAN SPONTANEOUS BEATING AFTER 2 WEEKS, AND EXPRESSED ANP AND BNP. ELECTRON MICROSCOPY REVEALED A CARDIOMYOCYTE-LIKE ULTRASTRUCTURE. THESE CELLS HAD SEVERAL TYPES OF ACTION POTENTIALS; SINUS NODE-LIKE AND VENTRICULAR CELL-LIKE ACTION POTENTIALS. THE ISOFORM OF CONTRACTILE PROTEIN GENES INDICATED THAT THEIR MUSCLE PHENOTYPE WAS SIMILAR TO FETAL VENTRICULAR CARDIOMYOCYTES. THEY MUSCLE PHENOTYPE WAS SIMILAR TO FETAL VENTRICULAR CARDIOMYOCYTES. THEY EXPRESSED □_<1A>, □_<1B>, □_<1D>, AND □_2 ADRENERGIC AND M1 AND M2 MUSCARINIC RECEPTORS. STIMULATION WITH PHENYLEPHRINE, ISOPROTERENOL AND CARBACHOL INCREASED ERK PHOSPHORYLATION AND SECOND MESSENGERS. ISOPROTERENOL INCREASED THE BEATING RATE, WHICH WAS BLOCKED WITH CGP20712A (□_1-SELECTIVE BLOCKER). THESE FINDINGS INDICATED THAT CELL TRANSPLANTATION THERAPY FOR THE PATIENTS WITH HEART FAILURE MIGHT POSSIBLY BE ACHIEVED USING THE REGENERATED CARDIOMYOCYTES FROM AUTOLOGOUS BONE MARROW CELLS IN THE NEAR FUTURE.

我们从小鼠骨髓间充质干细胞中分离出一个心肌细胞系（CMG细胞）。细胞呈成纤维细胞样形态，但5-氮胞苷暴露后形态发生变化。2周后开始自发性搏动，并表达ANP和BNP。电子显微镜显示心肌细胞样超微结构。这些细胞具有几种类型的动作电位;窦房结样和心室细胞样动作电位。心肌收缩蛋白基因的同源异型性表明其心肌表型与胎儿心室肌细胞相似。它们的肌肉表型与胎儿心室肌细胞相似。它们表达□_<1A>、□_<1B>、□_<1D>和□_2肾上腺素能受体以及M1和M2毒蕈碱受体。苯肾上腺素、异丙肾上腺素和卡巴胆碱均可增加ERK磷酸化和第二信使。异丙肾上腺素使搏动频率增加，CGP 20712 A（□_1-选择性阻断剂）阻断搏动频率。这些结果表明，用自体骨髓细胞再生的心肌细胞进行细胞移植治疗心力衰竭在不久的将来是可能实现的。

项目成果

小川 聡: "第98回日本内科学会講演会 教育講演 10.不整脈治療への新しいアプローチ"日本内科学会雑誌. 90. 245-250 (2001)

小川聪：“第98届日本内科医学会年会教育讲座10.心律失常治疗的新方法”日本内科医学会杂志90。245-250（2001）。

小川 聡: "心電図でどこまで読めるかCASE1健康診断で心室性期外収縮の多発を指摘された21歳女性"Heart View. 5. 145-148 (2001)

小川聪：“你能从心电图上读到多少信息？一位 21 岁的女性在 CASE1 健康检查中发现多次室性早搏”Heart View 5. 145-148 (2001)。

小川 聡: "負荷心電図から冠動脈病変をどこまで読める?心電図検査のコツと落とし穴"Pitfalls & Knack. 114-115 (2003)

小川聪：“通过负荷心电图您能了解多少冠状动脉病变？心电图的技巧和陷阱”Pitfalls & Knack 114-115 (2003)。

福田恵一: "心血管tissue engineeringを目指した再生心筋細胞の開発"心臓. 33. 47-50 (2001)

Keiichi Fukuda：“用于心血管组织工程的再生心肌细胞的开发”Heart. 33. 47-50 (2001)

Fukuda K, Makino S, Konishi F, Hakuno D, Manabe T, Ogawa S: "A Cardiomyocyte Cell Line Overcome Fibrotic Myocardium"Microcirculation annual (Nihon-Igakukan). 16. (2000)

Fukuda K、Makino S、Konishi F、Hakuno D、Manabe T、Okawa S：“克服纤维化心肌的心肌细胞系”微循环年鉴（Nihon-Igakukan）。