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基质胶诱导的小鼠组织工程腔室中脂肪组织的来源是宿主而非移植物。

Host rather than graft origin of Matrigel-induced adipose tissue in the murine tissue-engineering chamber.

作者信息

Stillaert Filip, Findlay Michael, Palmer Jason, Idrizi Rejhan, Cheang Shirley, Messina Aurora, Abberton Keren, Morrison Wayne, Thompson Erik W

机构信息

Bernard Brien Institute for Microsurgery, Melbourne, Victoria, Australia.

出版信息

Tissue Eng. 2007 Sep;13(9):2291-300. doi: 10.1089/ten.2006.0382.

Abstract

We have recently shown that Matrigel-filled chambers containing fibroblast growth factor-2 (FGF2) and placed around an epigastric pedicle in the mouse were highly adipogenic. Contact of this construct with pre-existing tissue or a free adipose graft was required. To further investigate the mechanisms underpinning formation of new adipose tissue, we seeded these chambers with human adipose biopsies and human adipose-derived cell populations in severe combined immunodeficient mice and assessed the origin of the resultant adipose tissue after 6 weeks using species-specific probes. The tissues were negative for human-specific vimentin labeling, suggesting that the fat originates from the murine host rather than the human graft. This was supported by the strong presence of mouse-specific Cot-1 deoxyribonucleic acid labeling, and the absence of human Cot-1 labeling in the new fat. Even chambers seeded with FGF2/Matrigel containing cultured human stromal-vascular fraction (SVF) labeled strongly only for human vimentin in cells that did not have a mature adipocyte phenotype; the newly formed fat tissue was negative for human vimentin. These findings indicate that grafts placed in the chamber have an inductive function for neo-adipogenesis, rather than supplying adipocyte-precursor cells to generate the new fat tissue, and preliminary observations implicate the SVF in producing inductive factors. This surprising finding opens the door for refinement of current adipose tissue-engineering approaches.

摘要

我们最近发现,在小鼠上腹部蒂周围放置含有成纤维细胞生长因子2(FGF2)的基质胶填充小室具有高度成脂性。这种构建体需要与预先存在的组织或游离脂肪移植物接触。为了进一步研究新脂肪组织形成的潜在机制,我们将人脂肪活检组织和人脂肪来源的细胞群体接种到严重联合免疫缺陷小鼠的这些小室中,并在6周后使用物种特异性探针评估所得脂肪组织的来源。这些组织的人特异性波形蛋白标记呈阴性,这表明脂肪来源于小鼠宿主而非人移植物。小鼠特异性Cot-1脱氧核糖核酸标记的大量存在以及新脂肪中缺乏人Cot-1标记支持了这一点。即使接种了含有培养的人基质血管成分(SVF)的FGF2/基质胶的小室,也仅在没有成熟脂肪细胞表型的细胞中强烈标记为人波形蛋白;新形成的脂肪组织中人波形蛋白呈阴性。这些发现表明,放置在小室中的移植物对新脂肪形成具有诱导作用,而不是提供脂肪前体细胞来生成新的脂肪组织,初步观察结果表明SVF参与产生诱导因子。这一惊人发现为改进当前的脂肪组织工程方法打开了大门。

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