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利用载有 SP(神经肽 P)和 SDF-1α(基质细胞衍生因子-1α)肽的血管移植物实现原位血管再生。

In Situ Blood Vessel Regeneration Using SP (Substance P) and SDF (Stromal Cell-Derived Factor)-1α Peptide Eluting Vascular Grafts.

机构信息

From the Department of Biomedical Engineering, Korea University of Science and Technology, Daejeon (M.S., S.H.K.).

Center for Biomaterials, Biomedical Research Institute, Department of Biomedical Engineering, Korea Institute of Science and Technology, Seoul, Republic of Korea (M.S., S.H.K.).

出版信息

Arterioscler Thromb Vasc Biol. 2018 Jul;38(7):e117-e134. doi: 10.1161/ATVBAHA.118.310934. Epub 2018 May 31.

DOI:10.1161/ATVBAHA.118.310934
PMID:29853570
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6039427/
Abstract

OBJECTIVE

The objective of this study was to develop small-diameter vascular grafts capable of eluting SDF (stromal cell-derived factor)-1α-derived peptide and SP (substance P) for in situ vascular regeneration.

APPROACH AND RESULTS

Polycaprolactone (PCL)/collagen grafts containing SP or SDF-1α-derived peptide were fabricated by electrospinning. SP and SDF-1α peptide-loaded grafts recruited significantly higher numbers of mesenchymal stem cells than that of the control group. The in vivo potential of PCL/collagen, SDF-1, and SP grafts was assessed by implanting them in a rat abdominal aorta for up to 4 weeks. All grafts remained patent as observed using color Doppler and stereomicroscope. Host cells infiltrated into the graft wall and the neointima was formed in peptides-eluting grafts. The lumen of the SP grafts was covered by the endothelial cells with cobblestone-like morphology, which were elongated in the direction of the blood flow, as discerned using scanning electron microscopy. Moreover, SDF-1α and SP grafts led to the formation of a confluent endothelium as evaluated using immunofluorescence staining with von Willebrand factor antibody. SP and SDF-1α grafts also promoted smooth muscle cell regeneration, endogenous stem cell recruitment, and blood vessel formation, which was the most prominent in the SP grafts. Evaluation of inflammatory response showed that 3 groups did not significantly differ in terms of the numbers of proinflammatory macrophages, whereas SP grafts showed significantly higher numbers of proremodeling macrophages than that of the control and SDF-1α grafts.

CONCLUSIONS

SDF-1α and SP grafts can be potential candidates for in situ vascular regeneration and are worthy for future investigations.

摘要

目的

本研究旨在开发能够洗脱 SDF(基质细胞衍生因子)-1α衍生肽和 SP(P 物质)的小直径血管移植物,用于原位血管再生。

方法和结果

通过静电纺丝制备了含有 SP 或 SDF-1α衍生肽的聚己内酯(PCL)/胶原蛋白移植物。与对照组相比,载有 SP 和 SDF-1α 肽的移植物募集了数量明显更多的间充质干细胞。通过将 PCL/胶原蛋白、SDF-1 和 SP 移植物植入大鼠腹主动脉长达 4 周来评估它们在体内的潜力。所有移植物均保持通畅,可通过彩色多普勒和立体显微镜观察到。宿主细胞浸润到移植物壁中,在肽洗脱移植物中形成了新生内膜。SP 移植物的管腔被具有鹅卵石状形态的内皮细胞覆盖,这些细胞在血流方向上伸长,可通过扫描电子显微镜观察到。此外,SDF-1α 和 SP 移植物导致形成了连续的内皮细胞,如用抗血管性血友病因子抗体进行免疫荧光染色所评估的那样。SP 和 SDF-1α 移植物还促进了平滑肌细胞再生、内源性干细胞募集和血管形成,在 SP 移植物中最为明显。炎症反应评估表明,3 组在促炎巨噬细胞的数量方面没有显著差异,而 SP 移植物显示出比对照组和 SDF-1α 移植物更高数量的促重塑巨噬细胞。

结论

SDF-1α 和 SP 移植物可能是原位血管再生的潜在候选物,值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/949b/6039427/183dba0179f7/atv-38-e117-g009.jpg
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