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首页> 外文期刊>Biomaterials >Dual delivery of VEGF and MCP-1 to support endothelial cell transplantation for therapeutic vascularization.
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Dual delivery of VEGF and MCP-1 to support endothelial cell transplantation for therapeutic vascularization.

机译：VEGF和MCP-1的双重递送可支持内皮细胞移植以治疗血管。

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Transplantation of endothelial cells (EC) for therapeutic vascularization is a promising approach in tissue engineering but has yet to be proven effective in clinical trials. This cell-based therapy is hindered by significant apoptosis of EC upon transplantation as well as poor recruitment of host mural cells to stabilize nascent vessels. Here, we address these deficiencies by augmenting endothelial cell transplantation with dual delivery of vascular endothelial growth factor (VEGF) - to improve survival of transplanted EC - and monocyte chemotactic protein-1 (MCP-1) - to induce mural cell recruitment. We produced alginate microparticles that deliver VEGF and MCP-1 with distinct release kinetics and that can be integrated into a collagen/fibronectin (protein) gel construct for delivery of EC. Combined delivery of VEGF and MCP-1 increased functional vessel formation from transplanted EC and also led to a higher number of smooth muscle cell-invested vessels than did EC therapy alone. Despite the well-known role of MCP-1 in inflammation, these beneficial effects were accomplished without a long-term increase in monocyte/macrophage recruitment or a shift to a pro-inflammatory (M1) macrophage phenotype. Overall, these data suggest a potential benefit of combined delivery of MCP-1 and VEGF from EC-containing hydrogels as a strategy for therapeutic vascularization.
机译：用于治疗性血管化的内皮细胞（EC）移植在组织工程中是一种有前途的方法，但尚未在临床试验中证明有效。这种基于细胞的疗法由于移植时EC的明显凋亡以及宿主壁细胞募集能力差而无法稳定新生血管而受到阻碍。在这里，我们通过用血管内皮生长因子（VEGF）的双重递送增强内皮细胞移植来解决这些缺陷-改善移植的EC的生存-单核细胞趋化蛋白1（MCP-1）-诱导壁细胞募集。我们生产了藻酸盐微粒，它们以不同的释放动力学传递VEGF和MCP-1，并且可以整合到胶原蛋白/纤连蛋白（蛋白质）凝胶构建物中以输送EC。与单独的EC治疗相比，VEGF和MCP-1的联合递送增加了移植EC的功能性血管形成，并导致更多的平滑肌细胞投资血管。尽管MCP-1在炎症中起着众所周知的作用，但这些有益效果的实现没有长期增加单核细胞/巨噬细胞募集或转移至促炎性（M1）巨噬细胞表型。总体而言，这些数据表明，从含EC的水凝胶中联合递送MCP-1和VEGF具有潜在的益处，可作为治疗性血管形成的策略。

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