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脂肪来源干细胞的抗皱作用:分泌因子对真皮成纤维细胞的激活

Antiwrinkle effect of adipose-derived stem cell: activation of dermal fibroblast by secretory factors.

作者信息

Kim Won-Serk, Park Byung-Soon, Park So-Hyun, Kim Hyung-Ki, Sung Jong-Hyuk

机构信息

Department of Dermatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

出版信息

J Dermatol Sci. 2009 Feb;53(2):96-102. doi: 10.1016/j.jdermsci.2008.08.007. Epub 2008 Oct 1.

Abstract

BACKGROUND

Adipose-derived stem cells (ADSC) have wound-healing and antioxidant effects on human skin via secretion of growth factors and activation of dermal fibroblasts.

OBJECTIVE

Paracrine mechanism reducing ultraviolet-B (UVB)-induced wrinkles by ADSC is investigated in this study.

METHODS AND RESULTS

Wrinkles were induced by an eight-week UVB irradiation, and were significantly improved by the subcutaneous injection of ADSC in hairless mice. In a replica analysis, parameters involving wrinkles were improved with mid-level and high doses of ADSC (1x10(4) and 1x10(5) cells). Dermal thickness and collagen contents in the dermis also were increased in the ADSC-injected groups. To characterize the paracrine mechanism involving the antiwrinkle effect of ADSC, a conditioned medium of ADSC (ADSC-CM) was directly incubated in human dermal fibroblasts (HDF). UVB irradiation reduced the proliferation of HDF, but this was reversed by the pretreatment of ADSC-CM in a dose-dependent manner. In a cell cycle analysis, ADSC-CM decreased the UVB-induced apoptotic cell death, which was demonstrated by the reduced sub-G1 phase of HDF. In addition, the ADSC-CM increased the protein expression of collagen type I and decreased the protein level of matrix metalloproteinase 1 in HDF, which may account for the increased collagen contents in the dermis.

CONCLUSIONS

Collectively, these results indicate that the ADSC and its secretory factors are effective for UVB-induced wrinkles, and the antiwrinkle effect is mainly mediated by reducing UVB-induced apoptosis and stimulating collagen synthesis of HDF.

摘要

背景

脂肪来源干细胞(ADSC)通过分泌生长因子和激活真皮成纤维细胞,对人体皮肤具有伤口愈合和抗氧化作用。

目的

本研究探讨ADSC减轻紫外线B(UVB)诱导皱纹的旁分泌机制。

方法与结果

通过八周的UVB照射诱导皱纹形成,在无毛小鼠中皮下注射ADSC可显著改善皱纹。在复制分析中,中剂量和高剂量的ADSC(1×10⁴和1×10⁵个细胞)可改善与皱纹相关的参数。注射ADSC的组中真皮厚度和真皮中的胶原蛋白含量也增加。为了表征涉及ADSC抗皱作用的旁分泌机制,将ADSC的条件培养基(ADSC-CM)直接与人真皮成纤维细胞(HDF)一起孵育。UVB照射降低了HDF的增殖,但ADSC-CM预处理以剂量依赖性方式逆转了这种情况。在细胞周期分析中,ADSC-CM减少了UVB诱导的凋亡细胞死亡,这通过HDF亚G1期的减少得到证明。此外,ADSC-CM增加了HDF中I型胶原蛋白的蛋白表达,并降低了基质金属蛋白酶1的蛋白水平,这可能解释了真皮中胶原蛋白含量的增加。

结论

总体而言,这些结果表明ADSC及其分泌因子对UVB诱导的皱纹有效,抗皱作用主要通过减少UVB诱导的细胞凋亡和刺激HDF的胶原蛋白合成来介导。

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