Dual delivery of VEGF and MCP-1 to support endothelial cell transplantation for therapeutic vascularization.
Dual delivery of VEGF and MCP-1 to support endothelial cell transplantation for therapeutic vascularization.
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DOI：
10.1016/j.biomaterials.2010.01.014
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发表时间：
2010-04
期刊：
影响因子：
14
通讯作者：
Saltzman, W. Mark
中科院分区：
文献类型：
--
作者：
Jay, Steven M.;Shepherd, Benjamin R.;Andrejecsk, Jillian W.;Kyriakides, Themis R.;Pober, Jordan S.;Saltzman, W. Mark
内皮细胞移植用于治疗性血管化是组织工程中一种有前途的方法，但尚未在临床试验中证明有效。这种基于细胞的治疗受到移植后EC的显著凋亡以及宿主壁细胞稳定新生血管的不良募集的阻碍。在这里，我们解决了这些缺陷，通过增强内皮细胞移植与血管内皮生长因子（VEGF）的双重交付-以提高移植EC的生存-和单核细胞趋化蛋白-1（MCP-1）-诱导壁细胞招聘。我们生产了藻酸盐微粒，其以不同的释放动力学递送VEGF和MCP-1，并且可以整合到胶原蛋白/纤连蛋白（蛋白质）凝胶构建体中用于递送EC。联合应用VEGF和MCP-1可增加移植EC的功能性血管形成，并且与单独应用EC治疗相比，还可导致更多的平滑肌细胞浸润血管。尽管MCP-1在炎症中的作用是众所周知的，但这些有益作用是在没有单核细胞/巨噬细胞募集的长期增加或向促炎（M1）巨噬细胞表型转变的情况下实现的。总的来说，这些数据表明从含EC的水凝胶组合递送MCP-1和VEGF作为治疗性血管形成的策略的潜在益处。
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.
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DOI：
10.1016/j.jconrel.2008.10.019
发表时间：
2009-02-20
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Jay SM;Saltzman WM
通讯作者：
Saltzman WM
影响因子：
20.3
作者：
Bhattacharya, V;McSweeney, PA;Wu, MHD
通讯作者：
Wu, MHD
影响因子：
15.9
作者：
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通讯作者：
Blau, HM
DOI：
10.1073/pnas.0408357102
发表时间：
2005-01-11
影响因子：
11.1
作者：
Enis, DR;Shepherd, BR;Schechner, JS
通讯作者：
Schechner, JS
影响因子：
6
作者：
Au, Patrick;Tam, Joshua;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.