Combination of in vivo angiopoietin-1 gene transfer and autologous bone marrow cell implantation for functional therapeutic angiogenesis

被引:43
作者
Kobayashi, Koichi
Kondo, Takahisa
Inoue, Natsuo
Aoki, Mika
Mizuno, Masaaki
Komori, Kimihiro
Yoshida, Jun
Murohara, Toyoaki
机构
[1] Nagoya Univ, Grad Sch Med, Dept Cardiol, Showa Ku, Nagoya, Aichi 4668550, Japan
[2] Nagoya Univ, Grad Sch Med, Dept Mol Neurosurg, Nagoya, Aichi, Japan
[3] Nagoya Univ, Grad Sch Med, Dept Vasc Surg, Nagoya, Aichi, Japan
[4] Nagoya Univ, Grad Sch Med, Dept Neurosurg, Nagoya, Aichi, Japan
关键词
angiogenesis; angiopoietin-1; bone marrow cells; vasculogenesis;
D O I
10.1161/01.ATV.0000223865.64812.26
中图分类号
R5 [内科学];
学科分类号
1002 [临床医学]; 100201 [内科学];
摘要
Objective - Autologous bone marrow mononuclear cell (BM-MNC) implantation into ischemic tissues promotes angiogenesis, but a large amount of marrow aspiration is required, which is a major clinical limitation. Angiopoietin-1 (Ang-1) is requisite for vascular maturation during angiogenesis. We examined the impacts of combinatorial Ang-1 gene transfer and low-dose autologous BM-MNC implantation on therapeutic angiogenesis in a rabbit model of hind limb ischemia. Methods and Results - Rabbits were divided into 4 groups: phosphate-buffered saline (control), 500 mu g Ang-1 plasmid (Ang-1), 1 x 10(6) autologous BM-MNCs (BMC), and Ang-1 plasmid plus BM-MNCs (combination). The Ang-1 group had a greater angiographic score and capillary density compared with the control (P < 0.05), but the Ang-1 gene therapy alone did not improve transcutaneous oxygen pressure (TcO2) and skin ulcer score. However, the combination group showed a significant improvement in not only angiographic score and capillary density (P < 0.05) but also TcO2 (P < 0.05) and skin ulcer score. These efficacies were greater in the combination group compared with the BMC group. Conclusions - This Ang-1 gene and BM-MNC combination therapy enhances not only quantitative but also qualitative angiogenesis in ischemic tissues. Moreover, the combination therapy will enable a reduction in the amount of BM aspiration required for significant therapeutic angiogenesis.
引用
收藏
页码:1465 / 1472
页数:8
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