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人脂肪来源干细胞在聚己内酯纤维基质上的脂肪生成增加。

Increased adipogenesis of human adipose-derived stem cells on polycaprolactone fiber matrices.

作者信息

Brännmark Cecilia, Paul Alexandra, Ribeiro Diana, Magnusson Björn, Brolén Gabriella, Enejder Annika, Forslöw Anna

机构信息

Reagent and Assay Development Discovery Sciences R&D, Astra Zeneca, Mölndal, Sweden.

Molecular Microscopy Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.

出版信息

PLoS One. 2014 Nov 24;9(11):e113620. doi: 10.1371/journal.pone.0113620. eCollection 2014.

Abstract

With accelerating rates of obesity and type 2 diabetes world-wide, interest in studying the adipocyte and adipose tissue is increasing. Human adipose derived stem cells--differentiated to adipocytes in vitro--are frequently used as a model system for white adipocytes, as most of their pathways and functions resemble mature adipocytes in vivo. However, these cells are not completely like in vivo mature adipocytes. Hosting the cells in a more physiologically relevant environment compared to conventional two-dimensional cell culturing on plastic surfaces, can produce spatial cues that drive the cells towards a more mature state. We investigated the adipogenesis of adipose derived stem cells on electro spun polycaprolactone matrices and compared functionality to conventional two-dimensional cultures as well as to human primary mature adipocytes. To assess the degree of adipogenesis we measured cellular glucose-uptake and lipolysis and used a range of different methods to evaluate lipid accumulation. We compared the averaged results from a whole population with the single cell characteristics--studied by coherent anti-Stokes Raman scattering microscopy--to gain a comprehensive picture of the cell phenotypes. In adipose derived stem cells differentiated on a polycaprolactone-fiber matrix; an increased sensitivity in insulin-stimulated glucose uptake was detected when cells were grown on either aligned or random matrices. Furthermore, comparing differentiation of adipose derived stem cells on aligned polycaprolactone-fiber matrixes, to those differentiated in two-dimensional cultures showed, an increase in the cellular lipid accumulation, and hormone sensitive lipase content. In conclusion, we propose an adipocyte cell model created by differentiation of adipose derived stem cells on aligned polycaprolactone-fiber matrices which demonstrates increased maturity, compared to 2D cultured cells.

摘要

随着全球肥胖率和2型糖尿病发病率的不断上升,对脂肪细胞和脂肪组织的研究兴趣也在增加。人脂肪来源干细胞——在体外分化为脂肪细胞——经常被用作白色脂肪细胞的模型系统,因为它们的大多数途径和功能与体内成熟脂肪细胞相似。然而,这些细胞并不完全等同于体内成熟脂肪细胞。与在塑料表面进行的传统二维细胞培养相比,将细胞置于更具生理相关性的环境中,可以产生空间线索,促使细胞向更成熟的状态发展。我们研究了脂肪来源干细胞在电纺聚己内酯基质上的脂肪生成,并将其功能与传统二维培养以及人原代成熟脂肪细胞进行了比较。为了评估脂肪生成的程度,我们测量了细胞的葡萄糖摄取和脂解,并使用了一系列不同的方法来评估脂质积累。我们将整组细胞的平均结果与通过相干反斯托克斯拉曼散射显微镜研究的单细胞特征进行了比较,以全面了解细胞表型。在聚己内酯纤维基质上分化的脂肪来源干细胞中,当细胞在排列或随机基质上生长时,检测到胰岛素刺激的葡萄糖摄取敏感性增加。此外,将脂肪来源干细胞在排列的聚己内酯纤维基质上的分化与在二维培养中的分化进行比较,结果显示细胞脂质积累和激素敏感性脂肪酶含量增加。总之,我们提出了一种通过脂肪来源干细胞在排列的聚己内酯纤维基质上分化而创建的脂肪细胞模型,与二维培养的细胞相比,该模型显示出更高的成熟度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/702e/4242727/6da415e86afb/pone.0113620.g001.jpg

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