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THERAPEUTIC ANGIOGENESIS INDUCED BY AUTOLOGOUS BONE MARROW CELLS IMPLANTATION FOR THE TREATMENT OF ISCHEMIC DISEASES

自体骨髓细胞植入诱导治疗性血管生成治疗缺血性疾病

基本信息

批准号：
13671391
负责人：
HAMANO Kimikazu
金额：
$ 2.24万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671391/
关键词：
therapeutic angiogenesis ischemic bone marrow cell stem cell blow flow cell implantation growth factor survival 細胞生存心機能投与経路

项目摘要

Therapeutic angiogenesis can be induced by the implantation of bone marrow mononuclear cells (BM-MNCs), but the best cell fraction in BM-MNCs and the best delivery road for inducing therapeutic angiogenesis kept unclear.At first, we investigated the roles of stem cell fractions in BM-MNCs in this treatment. Stem cells were separated from mature BM-MNCs of mice using the antibody to stem cell receptor (CD117). More than ten-fold higher levels of VEGF were secreted from the CD117^+ cells than from the CD117^- cells (P< 0.001) 14 days after culture. Most of the CD117^- cells died, but the CD117^+ cells grew well and differentiated into endothelial ceils within 14 days of culture. CD117^+ cells (2 x 10^5), CD117^- cells (9.8 x 10^6), and total BM-MNCs (1 x 10^7) were also implanted into the ischemic hindlimbs of mice. The blood perfusion of the ischemic hindlimbs was significantly higher in the CD117^+ cell-implanted mice than in the CD117^- cell-implanted mice (P<0.01), but did not differ significantly from the BM-MNCs cell-implanted mice, 14 days after treatment. These results indicated that CD117^+ stem cells play a key role in the therapeutic angiogenesis induced by bone marrow cell implantation.Then, we investigated the potency of therapeutic angiogenesis inducing by BM-MNCs using different delivery roads in an acute myocardium infarction model in rats. After the ligation of left ascending coronary artery, BM-MNCs (1 x 10^7) were given intramuscularly (IM group) or intravenously (IV group). The survival of BM-MNCs was better in the IM group than the IV group. Furthermore, both the blood flow of infarction area and the cardiac ejection fraction were significantly higher in the IM group than the IV group. These results indicated that the angiogenic potency inducing by BM-MNCs implantation was better by local intramuscularly injection than by intravenous delivery.

骨髓单个核细胞（bonemarrowmononuclearcells，BM-MNCs）的移植可以诱导治疗性血管生成，但BM-MNCs的最佳细胞组分和诱导治疗性血管生成的最佳途径尚不清楚。使用干细胞受体（CD 117）的抗体从小鼠的成熟BM-MNCs分离干细胞。培养14天后，CD 117 ^+细胞分泌的VEGF水平比CD 117 ^-细胞高10倍以上（P< 0.001）。大多数CD 117 ^-细胞死亡，但CD 117 ^+细胞生长良好，并在培养14天内分化为内皮细胞。还将CD 117 ^+细胞（2 x 10^5）、CD 117 ^-细胞（9.8 x 10^6）和总BM-MNC（1 x 10^7）植入小鼠缺血后肢。治疗后14天，CD 117 ^+细胞植入小鼠的缺血后肢血液灌注显著高于CD 117 ^-细胞植入小鼠（P<0.01），但与BM-MNCs细胞植入小鼠无显著差异。以上结果表明，CD 117 ^+干细胞在骨髓细胞移植诱导的治疗性血管生成中起关键作用。结扎左冠状动脉后，肌内（IM组）或静脉内（IV组）给予BM-MNCs（1 × 10^7）。IM组BM-MNCs的存活率高于IV组。IM组梗死区血流量和心脏射血分数均显著高于IV组。结果表明，局部肌肉注射BM-MNCs诱导血管生成的能力优于静脉注射。