Enhanced dermal wound neovascularization by targeted delivery of endothelial progenitor cells using an RGD-g-PLLA scaffold

Enhanced dermal wound neovascularization by targeted delivery of endothelial progenitor cells using an RGD-g-PLLA scaffold
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DOI:
10.1016/j.biomaterials.2009.03.053
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发表时间:
2009-08-01
期刊:
影响因子:
14
通讯作者:
Suh, Wonhee
Suh, Wonhee
中科院分区:
工程技术1区
文献类型:
--
作者:
Kim, Koung Li;Han, Dong Keun;Suh, Wonhee

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内皮祖细胞是促进缺血组织新生血管的内皮前体细胞,由于其对损伤部位的归巢能力差,存活率低,血管再生效果有限,因此各种生物合成支架已被用作细胞载体,以克服目前的细胞移植方法。然而,很少有平行研究直接比较种植在合成支架内的内皮祖细胞和通过用于内皮祖细胞治疗的传统移植技术输送的内皮细胞的疗效。为了解决这些问题,RGD-g-PLLA生物合成支架被开发出来用于靶向EPC的输送,并被发现成功地支持了EPC的体外生长和内皮功能。这种支架似乎也是很好的体内靶向递送内皮祖细胞的载体,因为它促进了小鼠皮肤创伤模型中的血管再生。此外,与皮内注射EPC的直接比较表明,RGD-g-PLLA支架靶向注射EPC在移植的EPC的定位、存活/保留以及血管修复能力方面优于传统的局部注射方法。这些结果表明,开发一种有效的干细胞输送系统可能有助于利用有限数量的干细胞最大限度地发挥组织修复效率,从而解决目前使用简单细胞注射或输注的干细胞疗法有限的临床成功。(C)2009爱思唯尔有限公司。保留所有权利。
Endothelial progenitor cells (EPCs), endothelial precursors that promote neovascularization in ischemic tissues, have shown the limited vascular regeneration efficacy due to their poor homing into injured sites and low survival, so that a variety of biosynthetic scaffolds have been employed as cell delivery vehicles to overcome the current cell transplantation methods. However, few paralleled studies that directly compare the efficacy of EPCs seeded within synthetic scaffolds to that of EPCs delivered by the conventional transplantation techniques used for EPC therapies have been performed. To address these issues, RGD-g-PLLA biosynthetic scaffold was developed for the targeted EPC delivery and was found to successfully support the in vitro growth and endothelial functions of EPCs. This scaffold also appeared to be good as in vivo targeted delivery carriers of EPCs as it promoted vascular regeneration in a murine dermal wound models. Furthermore, direct comparison with the intradermal EPC injection revealed that the targeted delivery of EPCs by using the RGD-g-PLLA scaffold was superior to their conventional local injection method in terms of the localization and survival/retention of the transplanted EPCs, and their vascular repairing potential. These results suggest that the development of an effective stem cell delivery system may help to maximize the tissue-repairing efficacy with a limited number of stem cells, thereby resolving the limited clinical success of current stem cell therapies that have utilized simple cell injections or infusions. (C) 2009 Elsevier Ltd. All rights reserved.