Release of angiogenic growth factors from cells encapsulated in alginate beads with bioactive glass
Release of angiogenic growth factors from cells encapsulated in alginate beads with bioactive glass
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DOI：
10.1016/j.biomaterials.2004.10.021
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发表时间：
2005-07-01
期刊：
影响因子：
14
通讯作者：
Day, RM
中科院分区：
文献类型：
--
作者：
Keshaw, H;Forbes, A;Day, RM
使用基因疗法或递送重组生长因子（如血管内皮生长因子（VEGF））来刺激治疗性血管生成的尝试未能在人体试验中证明明确的功效。生物活性玻璃刺激成纤维细胞分泌显著增加量的血管生成生长因子，因此在治疗性血管生成中具有许多潜在的应用。本研究的目的是评估是否有可能将特定数量的生物活性玻璃和成纤维细胞封装到藻酸盐珠中，藻酸盐珠将分泌能够刺激血管生成的生长因子。将人成纤维细胞（CCD-18 Co）包封在具有特定量的45 S5生物活性玻璃的藻酸盐珠中，并在培养基中孵育（0-17天）。收集条件培养基并测定VEGF或用于通过测量人真皮微血管内皮细胞的增殖来评估其刺激血管生成的能力。在第17天，将珠溶解，并测量珠保留的VEGF的量。与用0%或1%（w/v）45 S5生物活性玻璃颗粒包封的细胞相比，用含有0.01%和0.1%（w/v）45 S5生物活性玻璃颗粒的藻酸盐珠包封的成纤维细胞分泌增加量的VEGF。与不含玻璃颗粒的珠相比，含有0.01%和0.1%（w/v）45 S5生物活性玻璃的溶解的藻酸盐珠含有显著更多的VEGF（p < 0.01）。从含有0.1%（w/v）45 S5生物活性玻璃颗粒的藻酸盐珠收集的条件培养基显著增加内皮细胞增殖（p < 0.01）。本研究的结果表明，生物活性玻璃和成纤维细胞可以成功地纳入藻酸盐珠用于提供血管生成生长因子。通过进一步优化，该技术提供了一种用于刺激治疗性血管生成的新型递送装置。(C)2004 Elsevier Ltd.保留所有权利。
Attempts to stimulate therapeutic angiogenesis using gene therapy or delivery of recombinant growth factors, such as vascular endothelial growth factor (VEGF), have failed to demonstrate unequivocal efficacy in human trials. Bioactive glass stimulates fibroblasts to secrete significantly increased amounts of angiogenic growth factors and therefore has a number of potential applications in therapeutic angiogenesis. The aim of this study was to assess whether it is possible to encapsulate specific quantities of bioactive glass and fibroblasts into alginate beads, which will secrete growth factors capable of stimulating angiogenesis. Human fibroblasts (CCD- 18Co) were encapsulated in alginate beads with specific quantities of 45S5 bioactive glass and incubated in culture medium (0-17 days). The conditioned medium was collected and assayed for VEGF or used to assess its ability to stimulate angiogenesis by measuring the proliferation of human dermal microvascular endothelial cells. At 17 days the beads were lysed and the amount of VEGF retained by the beads measured. Fibroblasts encapsulated in alginate beads containing 0.01% and 0.1% (w/v) 45S5 bioactive glass particles secreted increased quantities of VEGF compared with cells encapsulated with 0% or 1%, (w/v) 45S5 bioactive glass particles. Lysed alginate beads containing 0.01% and 0.1% (w/v) 45S5 bioactive glass contained significantly more VEGF (p < 0.01) compared with beads containing no glass particles. Endothelial cell proliferation was significantly increased (p < 0.01) by conditioned medium collected from alginate beads containing 0.1% (w/v) 45S5 bioactive glass particles. The results of this study demonstrate that bioactive glass and fibroblasts can be successfully incorporated into alginate beads for use in delivering angiogenic growth factors. With further optimization, this technique offers a novel delivery device for stimulating therapeutic angiogenesis. (C) 2004 Elsevier Ltd. All rights reserved.