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.

我们从鼠骨髓间充质干细胞中分离出心肌细胞系（CMG 细胞），该细胞表现出成纤维细胞样形态，但在接触 5-氮杂胞苷 2 后形态发生变化。周，并表达的电子显微镜显示了心肌细胞样的超微结构；窦结样和心室细胞样的动作电位表明它们的收缩蛋白基因。肌肉表型与胎儿心室心肌细胞相似。它们表达 □_<1A>、□_<1B>、□_<1D> 和 □_2 肾上腺素能细胞以及 M1 和 M2。苯肾上腺素、异丙肾上腺素和卡巴酚刺激毒蕈碱受体会增加 ERK 磷酸化，而第二信使会增加跳动速率，而该速率被 CGP20712A（□_1-选择性阻断剂）所阻断。在不久的将来，使用自体骨髓细胞再生的心肌细胞可能可以实现对心力衰竭患者的细胞移植治疗。

项目成果

Miyazaki T, Ogawa S, Douglas P.Zipes: "Changes in Monophasic Action Potential Configuration and Prevalence of Ventricular Fibrillation During Regional Ischemia and Reperfusion in the Intact Canine Heart: Effect of Preconditioning Ischemia and Potassium Ch

Miyazaki T、Okawa S、Douglas P.Zipes：“完整犬心脏局部缺血和再灌注期间单相动作电位构型的变化和心室颤动的发生率：预处理缺血和钾离子的影响

Sato T, Mitamura H, Kurita Y, Takeshita A, Shinagawa K, Miyoshi S, Kanki H, Hara M, Takatsuki S, Soejima K, Ogawa S: "Recovery of elelctrophysiological parameters after conversation of chronic lone atrial fibrillation depends on its duration"Int J Cardiol

Sato T、Mitamura H、Kurita Y、Takeshita A、Shinakawa K、Miyoshi S、Kanki H、Hara M、Takatsuki S、Soejima K、Okawa S：“慢性孤立性心房颤动对话后电生理参数的恢复取决于其持续时间”

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）。

Kodama H, Fukuda K, Takahashi T, Sano M, Kato T, Tahara S, Ogawa S et al.: "Role of EGF Receptor and Pyk2 in Endothelin-1-induced ERK Activation in Rat Cardiomyocytes"Journal of Mol Cell Cardiology. 34. 139-150 (2002)

Kodama H、Fukuda K、Takahashi T、Sano M、Kato T、Tahara S、Okawa S 等人：“EGF 受体和 Pyk2 在大鼠心肌细胞内皮素-1 诱导的 ERK 激活中的作用”Mol Cell Cardiology 杂志。

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）。