Recruitment of mesenchymal stem cells and macrophages by dual release of stromal cell-derived factor-1 and a macrophage recruitment agent enhances wound closure

Recruitment of mesenchymal stem cells and macrophages by dual release of stromal cell-derived factor-1 and a macrophage recruitment agent enhances wound closure
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DOI:
10.1002/jbm.a.35635
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发表时间:
2016-04-01
影响因子:
4.9
通讯作者:
Tabata, Yasuhiko
Tabata, Yasuhiko
中科院分区:
工程技术3区
文献类型:
--
作者:
Kim, Yang-Hee;Tabata, Yasuhiko

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在这项研究中,小鼠皮肤缺损的伤口闭合的间充质干细胞(MSC)和巨噬细胞的募集方面进行了检查。对于细胞募集,将MSC募集剂的基质衍生因子-1(SDF-1)和巨噬细胞募集剂的鞘氨醇-1磷酸激动剂(SEW 2871)掺入明胶水凝胶中,然后以受控方式释放。当应用于小鼠的皮肤伤口缺损时,掺入混合的500 ng SDF-1和0.4、0.8或1.6 mg SEW 2871-胶束的明胶水凝胶比掺入SDF-1或磷酸盐缓冲盐水的明胶水凝胶招募了更高数量的MSC和巨噬细胞。然而,与掺入0.4、0.8或1.6 mg SEW 2871-胶束的那些水凝胶相比,掺入混合SDF-1和SEW 2871-胶束的水凝胶所募集的M1表型巨噬细胞的数量显著低至显著程度。另一方面,与其他水凝胶相比,植入含有SDF-1和0.4 mg SEW 2871-胶束的水凝胶3天后,M2巨噬细胞的数量显着增加。体内实验显示,掺入SDF-1和0.4 mg SEW 2871-胶束的水凝胶促进皮肤缺损的伤口闭合的程度显著强于掺入SEW 2871-胶束、SDF-1以及SDF-1和更高剂量的SEW 2871-胶束的混合物的水凝胶。结论:骨髓间充质干细胞和巨噬细胞的体内募集可能有助于皮肤创伤的组织再生。(c)2016 Wiley Periodicals,Inc. J Biomed Mater Res Part A:104A:942-956,2016.
In this study, the wound closure of mouse skin defects was examined in terms of recruitment of mesenchymal stem cells (MSC) and macrophages. For the cells recruitment, stromal derived factor-1 (SDF-1) of a MSC recruitment agent and sphingosine-1 phosphate agonist (SEW2871) of a macrophages recruitment agent were incorporated into gelatin hydrogels, and then released in a controlled fashion. When applied to a skin wound defect of mice, gelatin hydrogels incorporating mixed 500 ng SDF-1 and 0.4, 0.8, or 1.6 mg SEW2871-micelles recruited a higher number of both MSC and macrophages than those incorporating SDF-1 or phosphate buffered saline. However, the number of M1 phenotype macrophages for the hydrogel incorporating mixed SDF-1 and SEW2871-micelles recruited was remarkably low to a significant extent compared with that for those hydrogel incorporating 0.4, 0.8, or 1.6 mg SEW2871-micelles. On the other hand, the number of M2 macrophages 3 days after the implantation of the hydrogels incorporating SDF-1 and 0.4 mg SEW2871-micelles significantly increased compared with that for other hydrogels. In vivo experiments revealed the hydrogels incorporating SDF-1 and 0.4 mg SEW2871-micelles promoted the wound closure of skin defect to a significant stronger extent than those incorporating SEW2871-micelles, SDF-1, and a mixture of SDF-1 and higher doses of SEW2871-micelles. It is concluded that the in vivo recruitment of MSC and macrophages to the defects may contribute to the tissue regeneration of skin wound. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 942-956, 2016.