Li Tao-Sheng, Hamano Kimikazu, Nishida Masahiko, Hayashi Masanori, Ito Hiroshi, Mikamo Akihito, Matsuzaki Masunori
Division of Cardiovascular Surgery, Department of Medical Bioregulation, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Am J Physiol Heart Circ Physiol. 2003 Sep;285(3):H931-7. doi: 10.1152/ajpheart.01146.2002.
Therapeutic angiogenesis can be induced by the implantation of bone marrow mononuclear cells. We investigated the roles of mature mononuclear cell and stem cell fractions in bone marrow in this treatment. Although CD34 is the most popular marker for stem cell selection for inducing therapeutic angiogenesis, we separated CD117-positive cells (CD117+) from mature bone marrow mononuclear cells [CD117-negative cells (CD117-)] from mice using the antibody to the stem cell receptor, because some of the bone marrow stem cells that express CD117+ and CD34- might generate angiogenic cytokines and differentiate into endothelial cells. The angiogenic potency of CD117+ and CD117- cells was investigated in vitro and in vivo. Significantly higher levels of VEGF were secreted from the CD117+ cells than from the CD117- cells (P < 0.001). Most of the CD117- cells died, but the CD117+ cells grew well and differentiated into endothelial cells within 14 days of culture. The CD117+ cells survived and were incorporated in microvessels within 14 days of being implanted into the ischemic hindlimbs of mice, but the CD117- cells did not. The microvessel density and blood perfusion of the ischemic hindlimbs were significantly higher in the CD117+ cell-implanted mice than in the CD117- cell-implanted mice (P < 0.01). The microvessel density in ischemic hindlimbs was also significantly higher in the CD117+ cell-implanted mice than in the total bone marrow cell-implanted mice (P < 0.05). Thus CD117+ stem cells play a key role in the therapeutic angiogenesis induced by bone marrow cell implantation.
骨髓单个核细胞植入可诱导治疗性血管生成。我们研究了骨髓中成熟单核细胞和干细胞组分在该治疗中的作用。尽管CD34是诱导治疗性血管生成的干细胞选择中最常用的标志物，但我们使用针对干细胞受体的抗体从小鼠成熟骨髓单个核细胞[CD117阴性细胞（CD117-）]中分离出CD117阳性细胞（CD117+），因为一些表达CD117+和CD34-的骨髓干细胞可能产生血管生成细胞因子并分化为内皮细胞。对CD117+和CD117-细胞的血管生成能力进行了体外和体内研究。CD117+细胞分泌的VEGF水平明显高于CD117-细胞（P<0.001）。大多数CD117-细胞死亡，但CD117+细胞生长良好，并在培养14天内分化为内皮细胞。将CD117+细胞植入小鼠缺血后肢14天内，这些细胞存活并整合到微血管中，但CD117-细胞则没有。植入CD117+细胞的小鼠缺血后肢的微血管密度和血液灌注明显高于植入CD117-细胞的小鼠（P<0.01）。植入CD117+细胞的小鼠缺血后肢的微血管密度也明显高于植入全骨髓细胞的小鼠（P<0.05）。因此，CD117+干细胞在骨髓细胞植入诱导的治疗性血管生成中起关键作用。
