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肥胖供体来源的皮下和内脏脂肪间充质干细胞(ASCs)的干性和成骨及成脂潜能存在不同程度的损伤。

Stemness and osteogenic and adipogenic potential are differently impaired in subcutaneous and visceral adipose derived stem cells (ASCs) isolated from obese donors.

机构信息

IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.

出版信息

Int J Immunopathol Pharmacol. 2013 Jan-Mar;26(1 Suppl):11-21. doi: 10.1177/03946320130260S103.

Abstract

Today adipose tissue is not just considered as the primary energy storage organ, but it is also recognized as an important endocrine tissue and an abundant source of mesenchymal stem cells (adipose-derived stem cells, ASCs). During the last decade, several studies have provided preclinical data on the safety and efficacy of ASCs, supporting their use in cell-based therapy for regenerative medicine purposes. Little is known about the effect of obesity on ASCs properties. Since ASCs differentiation and proliferation are determined by their niche, the differences in body fat distribution and the obesity-related co-morbidities may have several consequences. In this study we compared ASCs of subcutaneous adipose tissue from obese (obS-ASCs) and non-obese (nS-ASCs) donors in order to compare their immunophenotype and osteogenic and adipogenic potential. Moreover, in order to evaluate the possible difference between subcutaneous and visceral fat, obS-ASCs were also compared to ASCs derived from visceral adipose tissue of the same obese donors (obV-ASCs). Our results show that subcutaneous and visceral ASCs derived from obese donors have an impaired cell proliferation, clonogenic ability and immunophenotype. Nevertheless, obS-ASCs are able to differentiate toward osteogenic and adipogenic lineages, although to a small extent with respect to non-obese donors, whereas obV-ASCs lose most of their stem cell characteristics, including multi-differentiation potential. Taken together our findings confirm that not all ASCs present the same behavior, most likely due to their biological microenvironment in vivo. The specific stimuli which can play a key role in ASCs impairment, including the effects of the obesity-related inflammation, should be further investigated to have a complete picture of the phenomenon.

摘要

如今,脂肪组织不仅被认为是主要的储能器官,还被认为是一种重要的内分泌组织和间充质干细胞(脂肪来源干细胞,ASCs)的丰富来源。在过去的十年中,多项研究提供了 ASC 安全性和有效性的临床前数据,支持将其用于基于细胞的再生医学治疗。关于肥胖对 ASC 特性的影响知之甚少。由于 ASC 的分化和增殖取决于其微环境,体脂分布的差异和肥胖相关的合并症可能会产生多种后果。在这项研究中,我们比较了肥胖(obS-ASCs)和非肥胖(nS-ASCs)供体的皮下脂肪组织中的 ASC,以比较它们的免疫表型和成骨和成脂潜能。此外,为了评估皮下脂肪和内脏脂肪之间的可能差异,我们还将 obS-ASCs 与来自同一肥胖供体的内脏脂肪组织衍生的 ASC(obV-ASCs)进行了比较。我们的结果表明,来自肥胖供体的皮下和内脏 ASC 具有受损的细胞增殖、克隆形成能力和免疫表型。尽管如此,obS-ASCs 能够向成骨和成脂谱系分化,尽管与非肥胖供体相比程度较小,而 obV-ASCs 则失去了大部分干细胞特性,包括多向分化潜能。总之,我们的研究结果证实并非所有 ASC 都具有相同的行为,这很可能是由于它们在体内的生物学微环境所致。包括肥胖相关炎症影响在内的特定刺激因素可能在 ASC 损伤中发挥关键作用,应该进一步研究,以全面了解这一现象。

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