Alginate hydrogels allow for bioactive and sustained release of VEGF-C and VEGF-D for lymphangiogenic therapeutic applications.
Alginate hydrogels allow for bioactive and sustained release of VEGF-C and VEGF-D for lymphangiogenic therapeutic applications.
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DOI：
10.1371/journal.pone.0181484
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Silva EA
中科院分区：
文献类型：
--
作者：
Campbell KT;Hadley DJ;Kukis DL;Silva EA
淋巴功能障碍与许多心血管疾病的进展有关，这是由于淋巴功能障碍在维持组织液内稳方面的作用。促进新的淋巴管(淋巴管生成)是一种通过恢复淋巴功能来逆转这些心血管疾病的有前途的策略。血管内皮生长因子(VEGF)成员VEGF-C和VEGF-D都是刺激淋巴管生成的有力候选者，尽管维持对这些因子的空间和时间控制是开发有效的治疗性淋巴管生成应用的挑战。可注射的藻酸盐水凝胶已用于许多血管生成因子的控制输送，包括血管内皮生长因子-A，以刺激新的血管生成。然而，这些可调水凝胶用于输送淋巴管生成因子的效用从未被仔细研究过。因此，这项研究的目的是利用离子交联的藻酸盐水凝胶来传递血管内皮生长因子-C和血管内皮生长因子-D，以用于潜在的淋巴管生成应用。我们发现淋巴管内皮细胞(LECs)对一过性表达VEGF-C和VEGF-D很敏感，但不同因素的反应不同。在恒定浓度的VEGF-C和较高的初始浓度下，LEC有丝分裂和发芽反应最强，而随着时间的推移，其初始浓度逐渐降低。此外，藻酸盐水凝胶提供了放射性标记的血管内皮生长因子-C和血管内皮生长因子-D的持续释放。最后，从这些水凝胶中释放的血管内皮生长因子C和血管内皮生长因子D在体内通过鸡绒毛膜尿囊膜(CAM)试验促进了与外源添加的生长因子和新的血管形成相似数量的LEC萌芽。总之，这些发现表明，藻酸盐水凝胶可以提供持续的和生物活性的释放血管内皮生长因子-C和血管内皮生长因子-D，这可能在治疗性淋巴管生成中应用。
Lymphatic dysfunction is associated with the progression of many cardiovascular disorders due to their role in maintaining tissue fluid homeostasis. Promoting new lymphatic vessels (lymphangiogenesis) is a promising strategy to reverse these cardiovascular disorders via restoring lymphatic function. Vascular endothelial growth factor (VEGF) members VEGF-C and VEGF-D are both potent candidates for stimulating lymphangiogenesis, though maintaining spatial and temporal control of these factors represents a challenge to developing efficient therapeutic lymphangiogenic applications. Injectable alginate hydrogels have been useful for the controlled delivery of many angiogenic factors, including VEGF-A, to stimulate new blood vasculature. However, the utility of these tunable hydrogels for delivering lymphangiogenic factors has never been closely examined. Thus, the objective of this study was to utilize ionically cross-linked alginate hydrogels to deliver VEGF-C and VEGF-D for potential lymphangiogenic applications. We demonstrated that lymphatic endothelial cells (LECs) are sensitive to temporal presentation of VEGF-C and VEGF-D but with different responses between the factors. The greatest LEC mitogenic and sprouting response was observed for constant concentrations of VEGF-C and a high initial concentration that gradually decreased over time for VEGF-D. Additionally, alginate hydrogels provided sustained release of radiolabeled VEGF-C and VEGF-D. Finally, VEGF-C and VEGF-D released from these hydrogels promoted a similar number of LEC sprouts as exogenously added growth factors and new vasculature in vivo via a chick chorioallantoic membrane (CAM) assay. Overall, these findings demonstrate that alginate hydrogels can provide sustained and bioactive release of VEGF-C and VEGF-D which could have applications for therapeutic lymphangiogenesis.
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影响因子：
3.7
作者：
Bronckaers A;Hilkens P;Fanton Y;Struys T;Gervois P;Politis C;Martens W;Lambrichts I
通讯作者：
Lambrichts I
DOI：
10.1073/pnas.95.24.14389
发表时间：
1998-11-24
影响因子：
11.1
作者：
Cao, YH;Linden, P;Alitalo, K
通讯作者：
Alitalo, K
影响因子：
4.6
作者：
Cimpean, Anca Maria;Seclaman, Edward;Ribatti, Domenico
通讯作者：
Ribatti, Domenico
DOI：
10.1016/j.pathophys.2009.07.006
发表时间：
2010-09-01
期刊：
Pathophysiology : the official journal of the International Society for Pathophysiology
影响因子：
--
作者：
Cui, Yingjie
通讯作者：
Cui, Yingjie
DOI：
10.1073/pnas.95.2.548
发表时间：
1998-01-20
影响因子：
11.1
作者：
Achen, MG;Jeltsch, M;Stacker, SA
通讯作者：
Stacker, SA