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Adipose-Derived Stem/Stromal Cells Recapitulate Aging Biomarkers and Show Reduced Stem Cell Plasticity Affecting Their Adipogenic Differentiation Capacity.
Cellular Reprogramming ( IF 1.2 ) Pub Date : 2019-07-12 , DOI: 10.1089/cell.2019.0010
Juliane-Susanne Jung 1 , Christin Volk 1 , Christina Marga 1 , Alexander Navarrete Santos 2 , Matthias Jung 3 , Dan Rujescu 3 , Anne Navarrete Santos 1
Affiliation  

Stromal mesenchymal stem cells (MSCs) have the capability to self-renew and can differentiate into multiple cell types of the mesoderm germ layer, but their properties are affected by molecular aging mechanisms. MSCs can be obtained from adipose tissue termed as adipose-derived stem/stromal cells (ASCs) representing a promising tool for studying age-related diseases in detail. ASCs from young (16 weeks) and old (>108 weeks) rabbits were successfully isolated and propagated. ASCs showed the typical morphology and stained positive for CD105, Vimentin, Collagenase 1A, and negative for CD14, CD90, and CD73, demonstrating their mesenchymal origin. ASCs expressed MSC markers, including MYC, KLF4, CHD1, REST, and KAT6A, whereas pluripotency-related genes, such as NANOG, OCT4, and SOX2, were not expressed. Aged ASCs showed altered protein and mRNA levels of APOE, ATG7, FGF2, PTEN, and SIRT1. Adipogenic differentiation of old visceral ASCs was significantly decreased compared with young visceral ASCs. We successfully established rabbit ASC cultures representing an in vitro model for the analysis of stem cell aging mechanisms. ASCs, obtained from old female rabbits, showed age- and source-specific alteration due to aging of the donor. Stem cell plasticity was altered with age as shown by reduced adipogenic differentiation capacity.

中文翻译:

脂肪衍生的干细胞/基质细胞概括了老化的生物标志物,并显示出降低的干细胞可塑性影响其成脂分化能力。

基质间充质干细胞(MSC)具有自我更新的能力,可以分化为中胚层胚层的多种细胞类型,但它们的特性受分子老化机制的影响。MSC可以从称为脂肪来源的干/基质细胞(ASC)的脂肪组织中获得,代表了详细研究与年龄有关的疾病的有前途的工具。成功分离并繁殖了来自幼兔(16周)和成年兔(> 108周)的ASC。ASC显示出典型的形态,对CD105,波形蛋白,胶原酶1A染色呈阳性,而对CD14,CD90和CD73染色呈阴性,表明它们是间充质来源。ASC表达MSC标记,包括MYC,KLF4,CHD1,REST和KAT6A,而多能性相关基因(如NANOG,OCT4和SOX2)未表达。老化的ASC显示APOE,ATG7,FGF2,PTEN和SIRT1的蛋白质和mRNA水平改变。与年轻内脏ASC相比,旧内脏ASC的成脂分化显着降低。我们成功建立了代表体外模型的兔ASC培养物,用于分析干细胞衰老机制。从成年雌兔中获得的ASC由于供体的衰老而显示出年龄和来源特异性的改变。干细胞可塑性随着年龄的增长而改变,如成脂分化能力下降所表明。由于供体的衰老,显示出特定于年龄和来源的改变。干细胞可塑性随着年龄的增长而改变,如成脂分化能力下降所表明。由于供体的衰老,显示出特定于年龄和来源的改变。干细胞可塑性随着年龄的增长而改变,如成脂分化能力下降所表明。
更新日期:2019-11-01
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