Therapeutic Cell-transplantation for Sever Heart Failure

治疗性细胞移植治疗严重心力衰竭

• 批准号: 13470271
• 负责人: KOMEDA Masashi
• 金额: $ 8.38万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470271/
• 关键词: cell transplantation; bone marrow stem cell; skeletal myoblast; heart failure; 骨格筋芽細胞移植; 線維芽細胞増殖因子(bFGF); 骨格筋筋芽細胞

This study aimed to develop the ideal procedure for cellular cardiomyoplasty for severe cardiac failure. Fetal cardiomyocyte (FCM) transplantation prevents but does not reverse cardiac remodeling in rats with chronic MI. However, prevascularization with bFGF-incorporated microspheres could enhance the benefits of FCM transplantation. FCM transplantation exerted preventive effects against late LV dilation and dysfunction after LV repair surgery.Autologous cells, such as skeletal myoblasts (SM) and bone marrow stem cells (BMSC), were more tolerant for ischemia as compared to CM. In the study of SM. transplantation to the MI heart, a large number of freshly-isolated neonatal SM can survive in the host heart and fully replace the infarcted myocardium with reverse LV remodelling in rats with MI. Intravenous (IV) and intramyocardial (IM) deliveries of BMSC transplantation. in mice were assessed echocardiographically and histologically in MI model and in dilated cardiomyopathy (DCM) model. Transplantation was performed either in acute or chronic phase. In acute phase, both IV and IM deliveries in BMSC transplantation were effective in both MI and DCM models, whereas in chronic phase, IM delivery was superior in. MI model, and IV administration was superior in DCM model.

本研究旨在开发治疗严重心力衰竭的理想的细胞性心肌成形术。胚胎心肌细胞(FCM)移植可预防但不能逆转慢性心肌梗死大鼠的心脏重构。然而，使用bFGF微球预血管化能提高FCM移植的益处。FCM移植对LV修复术后晚期的LV扩张和功能障碍具有预防作用，与CM相比，自体细胞如骨骼肌母细胞(SM)和骨髓干细胞(BMSC)对缺血的耐受性更强。在SM的研究中。移植到MI大鼠心脏后，大量新鲜分离的新生SM可以在宿主心脏存活，并完全取代MI大鼠的心肌梗死后的反向左室重构。骨髓间充质干细胞移植静脉(IV)和心肌(IM)分娩。在心肌梗死模型和扩张型心肌病(DCM)模型中进行超声心动图和组织学评估。移植分为急性期和慢性期。在急性期，骨髓间充质干细胞移植的静脉注射和肌肉注射在MI和DCM模型中均有效，而在慢性期，即时注射的效果更好。MI模型，静脉给药优于DCM模型。

项目成果

Sakakibara Y, Tambara K, Lu F, Nishina T, Sakaguchi G, Nishimura K, Komeda M: "Combined Procedure of Surgical Repair and Cell Transplantation for Left Ventricular Aneurysm : An Experimental Study."Circulation. 106. 193-197 (2002)

Sakakibara Y、Tambara K、Lu F、Nishina T、Sakaguchi G、Nishimura K、Komeda M：“左心室动脉瘤手术修复和细胞移植的联合手术：实验研究。”循环。

Keiichi Tambara, Yutaka Sakakibara, Masashi Komeda, et al.: "Transplanting cells for the treatment of cardiomyopathy."Cardiomyopathies and Heart Failure.. 481-489 (2003)

Keiichi Tambara、Yutaka Sakakibara、Masashi Komeda 等人：“移植细胞治疗心肌病。”心肌病和心力衰竭.. 481-489 (2003)

Sakakibara Y, Tambara K, Sakaguchi G, Tabata Y, Nishimura K, Komeda M: "Toward surgical angiogenesis using slow-released basic fibroblast growth factor"Eur J Cardiothorac Surg.. (in press).

Sakakibara Y、Tambara K、Sakaguchi G、Tabata Y、Nishimura K、Komeda M：“利用缓慢释放的碱性成纤维细胞生长因子实现外科血管生成”Eur J Cardiothorac Surg..（出版中）。

Yutaka Sakakibara Hiroyuki Nakajima, Kazunobu Nishimura, et al.: "Comparison of efficacy between bone marrow cell transplantation and stem cell mobilization by G-CSF in post-infarct remodeling."Circulation. 108(Suppl IV). IV218 (2003)

Yutaka Sakakibara Hiroyuki Nakajima、Kazunobu Nishimura 等人：“骨髓细胞移植与 G-CSF 动员干细胞在梗塞后重塑中的功效比较。”循环。

Tambara K, Horii T, Komeda M, et al.: "Epicardial admonistration of control-released basic, fibroblast growth factor induces angiogenesis and improves left ventricular function in dilated cardiomyopathy"Circulation.. 108(Suppl IV). IV399 (2003)

Tambara K、Horii T、Komeda M 等人：“控制释放的碱性成纤维细胞生长因子的心外膜管理可诱导血管生成并改善扩张型心肌病的左心室功能”Cir​​culation.. 108（增补 IV）。