Treatment for chronic myocardial ischemia using autologous bone marrow derived mononuclear cells ; Therapeutic angiogenensis by myocardial injection catheter

使用自体骨髓来源的单核细胞治疗慢性心肌缺血；

• 批准号: 14570704
• 负责人: UENO Takafumi
• 金额: $ 2.56万
• 依托单位: KURUME UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570704/
• 关键词: angiogenesis; bone marrow mononuclear cells; catheter-based injection; myocardial ischemia; 慢性心虚血; 自己骨髄単核球移植; 慢性心筋虚血

Purpose of this study is to test the hypothesis that transplantation of autologous bone marrow-derived mononuclear cells (BM-MNCs) into ischemic myocardium using a catheter-based approach might augment neovascularization and promote recovery of ventricular function. Animals were injected with either saline or BM-MNCs into the ischemic area using an intramyocardial injection catheter. BM-MNCs were isolated using a cell density gradient method. Two groups of pigs received intramyocardial injections of either BM-MNCs (n=5) or saline (n=5). Neither contrast angiography of collateral flow nor echocardiographic wall motion scores during dobutamine stress were different between the groups at baseline, 4 weeks post treatment, improvement in wall motion was not seen in the treatment group during peak stress. Myocardial blood flow in the ischemic region was significantly increased from baseline for pigs receiving BM-MNCs (0.31_0.65ml/min/g). The capillary density in the ischemic area was significantly higher in myocardial tissue from pigs treated with BM-MNCs than in tissue from pigs treated with saline. In conclusion, transplantation of autologous BM-MNCs using an intramyocardial injection catheter contributed to angiogenesis and improved cardiac function in chronically ischemic myocardium in pigs.

本研究的目的是验证使用基于导管的方法将自体骨髓来源的单核细胞（BM-MNCs）移植到缺血心肌中可能增加新血管形成并促进心室功能恢复的假设。使用心肌内注射导管将生理盐水或BM-MNCs注射到动物的缺血区域。使用细胞密度梯度法分离BM-MNC。两组猪接受BM-MNCs（n=5）或盐水（n=5）的心肌内注射。两组在基线、治疗后4周时，多巴酚丁胺负荷时侧支血流造影和超声心动图室壁运动评分均无差异，治疗组在峰值负荷时室壁运动未见改善。对于接受BM-MNCs的猪，缺血区域中的心肌血流量从基线显著增加（0.31 - 0.65ml/min/g）。在缺血区域的毛细血管密度显着高于从用BM-MNCs处理的猪的心肌组织中的组织与盐水处理的猪。总之，使用心肌内注射导管移植自体BM-MNCs有助于猪慢性缺血心肌的血管生成和改善心功能。

项目成果

Shintani S.Murohara T, Ikeda H, Ueno T, Honma T, Katoh A, Sasaki K, Shiinada T, Oike Y, Imaizumi T.: "Mobilization of endothelial progenitor cells in patients with acute myocardial infarction."Circulation. 103. 2776-2779 (2001)

Shintani S.Murohara T、Ikeda H、Ueno T、Honma T、Katoh A、Sasaki K、Shiinada T、Oike Y、Imaizumi T.：“急性心肌梗塞患者内皮祖细胞的动员。”循环。

Li J, De Leon H, Ueno T, Chronos NA, Robinson KA.: "Vasomotor function of pig coronary arteries after chronic coronary occlusion."J Cardiovasc Pharmacol. 41. 600-608 (2003)

Li J、De Leon H、Ueno T、Chronos NA、Robinson KA.：“慢性冠状动脉闭塞后猪冠状动脉的血管舒缩功能。”J Cardiovasc Pharmacol。

Katoh A, Ikeda H, Takajo Y, Haramaki N, Murohara T, Shintani S, Kanaya S, Yokoyama S, Ueno T, Homna T, Imaizumi T.: "Coexistence of impairment of endothelium-derived nitric oxide and platelet-derived nitric oxide in patients with coronary risk factors."Ci

Katoh A、Ikeda H、Takajo Y、Haramaki N、Murohara T、Shintani S、Kanaya S、Yokoyama S、Ueno T、Homna T、Imaizumi T.：“内皮源性一氧化氮和血小板源性一氧化氮损伤的共存

Shintani S,Murohara T,Ikeda H,Ueno T,Sasaki K,Duan J,& Imaizumi T.: "Augmentation of postnatal neovascularization with autologous bone marrow transplantation."Circulation.. 103. 897-903 (2001)

Shintani S,Murohara T,Ikeda H,Ueno T,Sasaki K,Duan J,

Shintani S, Murohara T, Ikeda H, Ueno T, Sasaki K, Imaizumi T.: "Augmentation of postnatal neovascularization with autologous bone marrow transplantation."Circulation. 103. 897-903 (2001)

Shintani S、Murohara T、Ikeda H、Ueno T、Sasaki K、Imaizumi T.：“通过自体骨髓移植增强产后新生血管。”循环。