Proangiogenic cells enhanced persistent and physiologic neovascularization compared with macrophages.
Proangiogenic cells enhanced persistent and physiologic neovascularization compared with macrophages.
复制标题
与巨噬细胞相比，促血管生成细胞增强了持久性和生理新生血管化。
DOI：
10.1038/emm.2015.60
复制
发表时间：
2015-09-25
影响因子：
12.8
通讯作者：
Yoon CH
中科院分区：
文献类型：
--
作者：
Choi YE;Cha YR;Lee KM;Kim HJ;Yoon CH
促血管生成细胞（PAC）显示表面标志物，并分泌类似于骨髓单核细胞所使用的血管生成因子，但与骨髓单核细胞不同，PAC增强实验性缺血性疾病中的新血管形成活性。本研究旨在揭示PAC与骨髓单核细胞相比的差异性新生血管活性。我们将PAC和CD 14+衍生的巨噬细胞（Macs）培养7天。两种细胞类型中的大多数表面标志物和细胞因子相似; KDR、β8整联蛋白、白细胞介素-8和单核细胞趋化蛋白-1除外。与Mac不同，PAC显着增强了间充质干细胞（MSC）的迁移。PAC和MAC增加了人脐静脉内皮细胞和MSC的体外共培养物中的新血管形成活性，以及在Matrigel中的体内共移植中的新血管形成活性。然而，使用MAC会导致血管扩张不当和渗漏，而使用PAC则不会。我们在裸鼠中诱导严重后肢缺血，然后将PAC、MAC或溶剂移植到小鼠中。我们每周获得激光多普勒灌注图像。在2周时，用PAC治疗的小鼠显示出与用MAC治疗的小鼠相比显著增强的灌注恢复。第7天后，当细胞耗尽使用自杀基因，病毒胸苷激酶，诱导细胞凋亡的细胞在体内更昔洛韦管理，我们发现，改善灌注显着废除在PAC治疗组，而灌注没有改变在Mac治疗组。PAC在体外和体内血管生成模型中引起健康新血管的增加，并在后肢缺血模型中增强长期功能性新血管形成活性，而MAC则没有。然而，应验证特定细胞类型的血管生成潜力和长期功能结果，以确认该细胞类型用于治疗性血管生成程序的有效性和安全性。
Proangiogenic cells (PACs) display surface markers and secrete angiogenic factors similar to those used by myelomonocytic cells, but, unlike myelomonocytic cells, PACs enhance neovascularization activity in experimental ischemic diseases. This study was performed to reveal the differential neovascularization activities of PACs compared with those of myelomonocytic cells. We cultured PACs and CD14+-derived macrophages (Macs) for 7 days. Most of the surface markers and cytokines in the two cell types were alike; the exceptions were KDR, β8 integrin, interleukin-8 and monocyte chemotactic protein-1. Unlike Macs, PACs significantly enhanced mesenchymal stem cell (MSC) transmigration. PACs and Macs increased neovascularization activity in an in vitro co-culture of human umbilical vein endothelial cells and MSCs and in an in vivo cotransplantation in Matrigel. However, the use of Macs resulted in inappropriately dilated and leaky vessels, whereas the use of PACs did not. We induced critical hindlimb ischemia in nude mice, and then transplanted PACs, Macs or vehicle into the mice. We obtained laser Doppler perfusion images weekly. At 2 weeks, mice treated with PACs showed significantly enhanced perfusion recovery in contrast to those treated with Macs. After day 7, when cells were depleted using a suicidal gene, viral thymidine kinase, to induce apoptosis of the cells in vivo by ganciclovir administration, we found that the improved perfusion was significantly abrogated in the PAC-treated group, whereas perfusion was not changed in the Mac-treated group. PACs caused an increase in healthy new vessels in in vitro and in vivo models of angiogenesis and enhanced long-term functional neovascularization activity in the hindlimb ischemia model, whereas Macs did not. Nevertheless, the angiogenic potential and long-term functional results for a specific cell type should be validated to confirm effectiveness and safety of the cell type for use in therapeutic angiogenesis procedures.