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基质细胞衍生生长因子-1α-弹性蛋白样肽融合蛋白促进糖尿病小鼠实验性伤口的细胞迁移和血管再生。

Stromal Cell-Derived Growth Factor-1 Alpha-Elastin Like Peptide Fusion Protein Promotes Cell Migration and Revascularization of Experimental Wounds in Diabetic Mice.

作者信息

Yeboah Agnes, Maguire Tim, Schloss Rene, Berthiaume Francois, Yarmush Martin L

机构信息

Department of Chemical and Biochemical Engineering, Rutgers University , Piscataway, New Jersey.

Department of Biomedical Engineering, Rutgers University , Piscataway, New Jersey.

出版信息

Adv Wound Care (New Rochelle). 2017 Jan 1;6(1):10-22. doi: 10.1089/wound.2016.0694.

Abstract

In previous work, we demonstrated the development of a novel fusion protein containing stromal cell-derived growth factor-1 alpha juxtaposed to an elastin-like peptide (SDF1-ELP), which has similar bioactivity, but is more stable in elastase than SDF1. Herein, we compare the ability of a single topical application of SDF1-ELP to that of SDF1 in healing 1 × 1 cm excisional wounds in diabetic mice. Human Leukemia-60 cells were used to demonstrate the chemotactic potential of SDF1-ELP versus SDF1 . Human umbilical vascular endothelial cells were used to demonstrate the angiogenic potential of SDF1-ELP versus SDF1 . The bioactivity of SDF1-ELP versus SDF1 after incubation in diabetic wound fluid was compared. The effectiveness of SDF1-ELP versus SDF1 was compared in diabetic mice wound model by monitoring for the number of CD31+ cells in harvested wound tissues. SDF1-ELP promotes the migration of cells and induces vascularization similar to SDF1 . SDF1-ELP is more stable in wound fluids compared to SDF1. , SDF1-ELP induced a higher number of vascular endothelial cells (CD31+ cells) compared to SDF1 and other controls, suggesting increased vascularization. While growth factors have been shown to improve wound healing, this strategy is largely ineffective in chronic wounds. In this work, we show that SDF1-ELP is a promising agent for the treatment of chronic skin wounds. The superior performance and stability of SDF1-ELP makes it a promising agent for the treatment of chronic skin wounds.

摘要

在之前的工作中,我们展示了一种新型融合蛋白的研发,该蛋白包含与弹性蛋白样肽并列的基质细胞衍生生长因子-1α(SDF1-ELP),它具有相似的生物活性,但在弹性蛋白酶中比SDF1更稳定。在此,我们比较了单次局部应用SDF1-ELP和SDF1对糖尿病小鼠1×1厘米切除伤口愈合的能力。使用人白血病-60细胞来证明SDF1-ELP与SDF1相比的趋化潜力。使用人脐血管内皮细胞来证明SDF1-ELP与SDF1相比的血管生成潜力。比较了SDF1-ELP与SDF1在糖尿病伤口液中孵育后的生物活性。通过监测收获的伤口组织中CD31+细胞的数量,在糖尿病小鼠伤口模型中比较了SDF1-ELP与SDF1的有效性。SDF1-ELP促进细胞迁移并诱导血管生成,类似于SDF1。与SDF1相比,SDF1-ELP在伤口液中更稳定。与SDF1和其他对照相比,SDF1-ELP诱导出更多的血管内皮细胞(CD31+细胞),表明血管生成增加。虽然生长因子已被证明可改善伤口愈合,但这种策略在慢性伤口中大多无效。在这项工作中,我们表明SDF1-ELP是治疗慢性皮肤伤口的一种有前景的药物。SDF1-ELP的卓越性能和稳定性使其成为治疗慢性皮肤伤口的一种有前景的药物。

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