Human adult vena saphena contains perivascular progenitor cells endowed with clonogenic and proangiogenic potential.
Human adult vena saphena contains perivascular progenitor cells endowed with clonogenic and proangiogenic potential.
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DOI：
10.1161/circulationaha.109.899252
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发表时间：
2010-04-20
期刊：
影响因子：
37.8
通讯作者：
Madeddu P
中科院分区：
文献类型：
--
作者：
Campagnolo P;Cesselli D;Al Haj Zen A;Beltrami AP;Kränkel N;Katare R;Angelini G;Emanueli C;Madeddu P
在缺血性患者中进行的临床试验表明了自体骨髓祖细胞移植的安全性和益处。具有促血管生成能力的非骨髓祖细胞已有相关描述，但由于其稀缺性、获取困难以及体外扩增能力低，在临床上尚未得到应用。我们研究了接受冠状动脉搭桥手术患者的大隐静脉中祖细胞的存在情况、抗原特征、扩增能力以及促血管生成潜力。
内皮标记物血管性血友病因子阴性的CD34阳性细胞位于外膜血管滋养管周围。在将静脉从周围组织中分离并进行酶消化后，通过选择性培养、免疫磁珠或荧光辅助细胞分选技术分离出CD34阳性/CD31阴性细胞。在有血清存在的情况下，CD34阳性/CD31阴性细胞产生了一个高度增殖的群体，该群体表达周细胞/间充质抗原以及干细胞标记物Sox2，并显示出克隆形成和多向分化能力。我们将这个群体称为“大隐静脉来源的祖细胞”（SVPs）。在培养过程中，SVPs整合到内皮细胞形成的网络中，并通过旁分泌机制促进血管生成。反过来，内皮细胞释放的因子促进了SVP的迁移。这些相互作用可被Tie - 2或血小板衍生生长因子 - BB阻断所抑制。在免疫缺陷小鼠的缺血肢体中肌肉注射SVPs可改善新生血管形成和血流恢复。在移植后14天，在受体肌肉中仍可检测到增殖的SVPs，它们在那里与毛细血管内皮建立了N - 钙黏蛋白介导的物理接触。
由人静脉CD34阳性/CD31阴性祖细胞产生的SVPs可能代表了一种用于缺血性患者血管生成治疗的新治疗工具。
Clinical trials in ischemic patients showed the safety and benefit of autologous bone marrow progenitor cell transplantation. Non–bone marrow progenitor cells with proangiogenic capacities have been described, yet they remain clinically unexploited owing to their scarcity, difficulty of access, and low ex vivo expansibility. We investigated the presence, antigenic profile, expansion capacity, and proangiogenic potential of progenitor cells from the saphenous vein of patients undergoing coronary artery bypass surgery. CD34-positive cells, negative for the endothelial marker von Willebrand factor, were localized around adventitial vasa vasorum. After dissection of the vein from surrounding tissues and enzymatic digestion, CD34-positive/CD31-negative cells were isolated by selective culture, immunomagnetic beads, or fluorescence-assisted cell sorting. In the presence of serum, CD34-positive/CD31-negative cells gave rise to a highly proliferative population that expressed pericyte/mesenchymal antigens together with the stem cell marker Sox2 and showed clonogenic and multilineage differentiation capacities. We called this population “saphenous vein–derived progenitor cells” (SVPs). In culture, SVPs integrated into networks formed by endothelial cells and supported angiogenesis through paracrine mechanisms. Reciprocally, endothelial cell–released factors facilitated SVP migration. These interactive responses were inhibited by Tie-2 or platelet-derived growth factor-BB blockade. Intramuscular injection of SVPs in ischemic limbs of immunodeficient mice improved neovascularization and blood flow recovery. At 14 days after transplantation, proliferating SVPs were still detectable in the recipient muscles, where they established N-cadherin–mediated physical contact with the capillary endothelium. SVPs generated from human vein CD34-positive/CD31-negative progenitor cells might represent a new therapeutic tool for angiogenic therapy in ischemic patients.