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LGR6+ 上皮干细胞移植到全层皮肤创伤可促进愈合、新生毛囊发育,并增加血管生成分析物。

Transplantation of the LGR6+ epithelial stem cell into full-thickness cutaneous wounds results in enhanced healing, nascent hair follicle development, and augmentation of angiogenic analytes.

机构信息

Springfield, Ill.; and Baltimore, Md. From the Department of Surgery, Institute for Plastic Surgery, Microsurgery and Tissue Engineering Laboratory, Southern Illinois University; and the Departments of Plastic Surgery and Biological Chemistry, The Johns Hopkins University Hospital.

出版信息

Plast Reconstr Surg. 2014 Mar;133(3):579-590. doi: 10.1097/PRS.0000000000000075.

Abstract

BACKGROUND

The recently discovered leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6+) epithelial stem cell located within the follicular bulge of the adnexal compartment is capable of producing all cellular lineages of the skin. In this study, the authors sought to determine whether these cells can be transplanted for use as a type of cellular therapy for the repair of full-thickness wounds in which the native stem cell niche has been obliterated.

METHODS

Full-thickness murine skin was harvested and LGR6(+GFP) epithelial stem cells were isolated using fluorescence-activated cell sorting. This enriched epithelial stem cell population was then transplanted by means of local injection into wound beds on the dorsum of nude mice. Viability, migration, healing, the development of nascent hair follicles, and gene and proteomic expression studies were performed to determine whether the engraftment of LGR6(+GFP) epithelial stem cells enhanced healing when compared with controls.

RESULTS

Wound beds receiving LGR6(+GFP) epithelial stem cells showed enhanced healing; nascent follicle growth; and augmentation of the Wnt, vascular endothelial growth factor, epidermal growth factor, and platelet-derived growth factor pathways when compared with controls.

CONCLUSIONS

The LGR6+ epithelial stem cells appear to hold great promise for the development of a clinically useful stem cell–based therapy for the repair of full-thickness wounds and hair regeneration. These results indicate that transplantation of LGR6+ epithelial stem cells promotes epithelialization, hair growth, and angiogenesis in tissues destined for scar formation.

摘要

背景

最近发现的富含亮氨酸重复序列的 G 蛋白偶联受体 6(LGR6+)上皮干细胞位于附属器间隔的毛囊隆起处,能够产生皮肤的所有细胞谱系。在这项研究中,作者试图确定这些细胞是否可以被移植用于修复全层皮肤缺损,其中天然干细胞龛已被破坏的细胞治疗。

方法

采集全层鼠皮,用荧光激活细胞分选术分离 LGR6(+GFP)上皮干细胞。然后通过局部注射将这种富集的上皮干细胞群体移植到裸鼠背部的创面床上。进行了生存能力、迁移、愈合、新生毛囊的发育以及基因和蛋白质组学表达研究,以确定与对照组相比,LGR6(+GFP)上皮干细胞的植入是否增强了愈合。

结果

与对照组相比,接受 LGR6(+GFP)上皮干细胞的创面床显示出增强的愈合;新生毛囊生长;以及 Wnt、血管内皮生长因子、表皮生长因子和血小板衍生生长因子途径的增强。

结论

LGR6+上皮干细胞似乎为开发基于干细胞的临床有用疗法以修复全层皮肤缺损和毛发再生提供了巨大的希望。这些结果表明,移植 LGR6+上皮干细胞可促进组织中的上皮化、毛发生长和血管生成,防止形成瘢痕。

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