Kondo Kazuhisa, Shintani Satoshi, Shibata Rei, Murakami Hisashi, Murakami Ryuichiro, Imaizumi Masayasu, Kitagawa Yasuo, Murohara Toyoaki
Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, 466-8550 Japan.
Arterioscler Thromb Vasc Biol. 2009 Jan;29(1):61-6. doi: 10.1161/ATVBAHA.108.166496. Epub 2008 Oct 30.
Therapeutic angiogenesis using autologous stem/progenitor cells represents a novel strategy for severe ischemic diseases. Recent reports indicated that adipose tissues could supply adipose-derived regenerative cells (ADRCs). Accordingly, we examined whether implantation of ADRCs would augment ischemia-induced angiogenesis.
Adipose tissue was obtained from C57BL/6J mice, and ADRCs were isolated using standard methods. ADRCs expressed stromal cell-derived factor 1 (SDF-1) mRNA and proteins. Hind limb ischemia was induced and culture-expanded ADRCs, PBS, or mature adipocytes (MAs) as control cells were injected into the ischemic muscles. At 3 weeks, the ADRC group had a greater laser Doppler blood perfusion index and a higher capillary density compared to the controls. Implantation of ADRCs increased circulating endothelial progenitor cells (EPCs). SDF-1 mRNA abundance at ischemic tissues and serum SDF-1 levels were greater in the ADRC group than in the control group. Finally, intraperitoneal injection of an anti-SDF-1 neutralizing antibody reduced the number of circulating EPCs and therapeutic efficacies of ADRCs.
Adipose tissue would be a valuable source for cell-based therapeutic angiogenesis. Moreover, chemokine SDF-1 may play a pivotal role in the ADRCs-mediated angiogenesis at least in part by facilitating mobilization of EPCs.
利用自体干细胞/祖细胞进行治疗性血管生成是治疗严重缺血性疾病的一种新策略。最近的报告表明，脂肪组织可以提供脂肪来源的再生细胞（ADRCs）。因此，我们研究了植入ADRCs是否会增强缺血诱导的血管生成。
从C57BL/6J小鼠获取脂肪组织，采用标准方法分离ADRCs。ADRCs表达基质细胞衍生因子1（SDF-1）的mRNA和蛋白。诱导后肢缺血，并将培养扩增的ADRCs、PBS或作为对照细胞的成熟脂肪细胞（MAs）注射到缺血肌肉中。3周时，与对照组相比，ADRCs组的激光多普勒血流灌注指数更高，毛细血管密度更高。植入ADRCs可增加循环内皮祖细胞（EPCs）。ADRCs组缺血组织中SDF-1 mRNA丰度和血清SDF-1水平高于对照组。最后，腹腔注射抗SDF-1中和抗体可减少循环EPCs的数量以及ADRCs的治疗效果。
脂肪组织将是基于细胞的治疗性血管生成的宝贵来源。此外，趋化因子SDF-1可能至少部分通过促进EPCs的动员在ADRCs介导的血管生成中起关键作用。
