Local Delivery of VEGF and SDF Enhances Endothelial Progenitor Cell Recruitment and Resultant Recovery from Ischemia
Local Delivery of VEGF and SDF Enhances Endothelial Progenitor Cell Recruitment and Resultant Recovery from Ischemia
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DOI：
10.1089/ten.tea.2014.0508
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发表时间：
2015-04-01
影响因子：
4.1
通讯作者：
Mooney, David J.
中科院分区：
文献类型：
--
作者：
Anderson, Erin M.;Kwee, Brian J.;Mooney, David J.
生物材料可能改善基于内皮祖细胞的治疗缺血性心血管疾病的结果，因为它们有能力指导细胞行为。我们假设海藻酸盐水凝胶中外源性血管内皮生长因子（VEGF）和基质细胞衍生因子（SDF）的局部持续递送可以增加全身输注的内皮祖细胞向缺血组织的募集，以及随后的新生血管形成。研究发现，VEGF和SDF可使两种内皮祖细胞（oec）和循环血管生成细胞（CACs）在体外的粘附和迁移能力提高2 - 6倍，在体内对缺血和非缺血肌肉组织的招募能力几乎增加一倍。局部给予缺血后肢VEGF和SDF与全身给予CAC相比，OEC给予或单独给予可显著改善功能灌注恢复。与oec相比，CACs对VEGF和SDF的反应更强，在体外更有效地促进了内皮芽的旁分泌形成，在体内对炎症细胞浸润的影响更大。这些研究表明，灌注内皮祖细胞的积累可以通过基于生物材料的VEGF和SDF的递送来富集，并强调了使用CACs治疗缺血的治疗益处。
Biomaterials may improve outcomes of endothelial progenitor-based therapies for the treatment of ischemic cardiovascular disease, due to their ability to direct cell behavior. We hypothesized that local, sustained delivery of exogenous vascular endothelial growth factor (VEGF) and stromal cell-derived factor (SDF) from alginate hydrogels could increase recruitment of systemically infused endothelial progenitors to ischemic tissue, and subsequent neovascularization. VEGF and SDF were found to enhance in vitro adhesion and migration of outgrowth endothelial cells (OECs) and circulating angiogenic cells (CACs), two populations of endothelial progenitors, by twofold to sixfold, and nearly doubled recruitment to both ischemic and nonischemic muscle tissue in vivo. Local delivery of VEGF and SDF to ischemic hind-limbs in combination with systemic CAC delivery significantly improved functional perfusion recovery over OEC delivery, or either treatment alone. Compared with OECs, CACs were more responsive to VEGF and SDF treatment, promoted in vitro endothelial sprout formation in a paracrine manner more potently, and demonstrated greater influence on infiltrating inflammatory cells in vivo. These studies demonstrate that accumulation of infused endothelial progenitors can be enriched using biomaterial-based delivery of VEGF and SDF, and emphasize the therapeutic benefit of using CACs for the treatment of ischemia.