Implementation of Regenerative Medicine (Analysis and Prophylaxis of Lethal Arrhythmias in Cell-Transplanted Heart)

再生医学的实施（细胞移植心脏致死性心律失常的分析和预防）

• 批准号: 16590675
• 负责人: SHIMIZU Atsuya
• 金额: $ 2.3万
• 依托单位: Nagoya 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 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590675/
• 关键词: myoblasts; cell transplantation; fusion cells; electrophysiological properties; arrhythmia; 電気生理学的な特性

Recently, cell-transplanted medicine is progressively advanced in order to regenerate diseased organs. In the field of cardiology, cardiac function has been demonstrated to be improved by the transplantation of multiple cells to the failured animal hearts. In human, cell-transplantation to the hearts often accompanied lethal arrhythmias, which is the main hurdle to implemement clinical application of cell transplantation therapy.In this study for two years, we studied the mechanisms of cardiac arrhythmias caused by cell transplantation of skeletal myoblasts in rabbit hearts. The first year, we clarified that, 1) In myoblasts, the restingmembrane potential was hyperpolarized around -100 mV and greatly reduced just before differentiation to myotubles, 2) the resting membrane of myotubles was around -40mV 3) muscle twitching was accompanied in myotubles, 4) myotubles were not electrically connected to adjacent cardiac cells. In the second year, we revealed that, 5) myotubles may electronically interfere excitation conduction in myocytes 6) cell fusion was rearely observed between myotubels and cardiac myocytes, 7) these fusion cells possess both characteristics of two types of originated cells.These data indicated that, transplanted cells which is electronically disconnected with adjacent cells may interfere excitation conduction of the heart, thereby leading to the lethal arrhythmias by augmentation of electrical inhomogeneity.

最近，细胞移植医学正在逐步发展，以再生患病器官。在心脏病学领域，已经证明通过向衰竭的动物心脏移植多种细胞来改善心脏功能。在人类心脏细胞移植中，常伴有致死性心律失常，这是细胞移植治疗临床应用的主要障碍，本研究历时两年，对骨骼肌成肌细胞移植兔心脏引起心律失常的机制进行了研究。第一年，我们阐明：1）成肌细胞静息膜电位在-100 mV左右超极化，在向肌管分化前显著降低; 2）肌管静息膜电位在-40 mV左右;第二年发现：5）肌管可能电干扰心肌细胞的兴奋传导; 6）肌管与心肌细胞之间很少观察到细胞融合; 7）融合细胞具有两种起源细胞的特征。这些数据表明，与相邻细胞电断开的移植细胞可能干扰心脏的兴奋传导，从而通过增加电不均匀性导致致命的心律失常。

项目成果

Pathyphysiological significance of T-type Ca^<2+> channels Expression of T-type Ca^<2+> channels in fetal and diseased heart.

T型Ca^2通道的病理生理学意义T型Ca^2通道在胎儿和患病心脏中的表达。

• 发表时间: 2005
• 期刊: Journal of Pharmacological Sciences 99
• 作者: Yasui K;et al.
• 通讯作者: et al.

Pathophysiological significance of T-type Ca2+ channels: expression of T-type Ca2+ channels in fetal and diseased heart.

• DOI: 10.1254/jphs.fmj05002x3
• 发表时间: 2005
• 期刊: Journal of pharmacological sciences
• 影响因子: 3.5
• 作者: K. Yasui;Noriko Niwa;Haruki Takemura;T. Opthof;Takao Muto;M. Horiba;A. Shimizu;Jong‐Kook Lee;H. Honjo;K. Kamiya;I. Kodama

Subtype switching of L-type Ca^<2+> channel from Cav1.3 to Cav1.2 in embryonic murine ventricle.

胚胎鼠心室中L型Ca^2通道从Cav1.3到Cav1.2的亚型转换。

• 发表时间: 2005
• 期刊: Circulation Journal 69
• 作者: Takemura H;et al.
• 通讯作者: et al.

Cav3.2 subunit underlies the functional T-type Ca2+ channel in murine hearts during the embryonic period

• DOI: 10.1152/ajpheart.01043.2003
• 发表时间: 2004-06-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
• 影响因子: 4.8
• 作者: Niwa, N;Yasui, K;Kodama, I
• 通讯作者: Kodama, I

Subtype switching of L-type Ca2+ channel from Cav1.3 to Cav1.2 in embryonic murine venticle.

胚胎鼠心室中 L 型 Ca2 通道从 Cav1.3 到 Cav1.2 的亚型转换。

• 发表时间: 2005
• 期刊: Circulation Journal 69
• 作者: Takemura H;et al.
• 通讯作者: et al.