Adipogenesis Induced by Human Adipose Tissue-Derived Stem Cells

Adipogenesis Induced by Human Adipose Tissue-Derived Stem Cells
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DOI:
10.1089/ten.tea.2007.0297
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发表时间:
2009-01-01
影响因子:
4.1
通讯作者:
Toi, Masakazu
Toi, Masakazu
中科院分区:
医学3区
文献类型:
--
作者:
Tsuji, Wakako;Inamoto, Takashi;Toi, Masakazu

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脂肪组织源性干细胞(ASC),包括前脂肪细胞,可能在脂肪从头生成中发挥重要作用,并有望成为脂肪组织工程的有用的外部细胞来源。在这项研究中,我们检查了植入后 24 周的体内脂肪生成,这是由从脂肪组织中分离并在体外扩增的人 ASC 诱导的。 ASCs在碱性成纤维细胞生长因子(bFGF)存在下在体外增殖,细胞数量在第四代时增加了1000倍以上。分化成成熟脂肪细胞的能力一直保持到第三代。我们将指定数量的第三代扩增细胞整合到 I 型胶原支架中,并将它们植入有或没有控释 bFGF 的裸鼠背部。植入2 x 10(6) ASC控释bFGF后,支架中脂肪组织的最大横截表面积在12周时为1.19 mm(2),在24周时为2.14 mm(2)。大约 2 x 10(6) ASC 与控释 bFGF 是总脂肪生成的最佳条件。使用抗人波形蛋白抗体进行的免疫组织化学分析表明,在第12周和第24周时,在支架中掺入8 x 10(6) ASCs的组中,人源脂肪组织的面积最大。从 12 周到 24 周,所有植入 ASC 的组中人源脂肪组织的数量均有所增加。在植入 ASC 的其他组中仅观察到痕量的人源脂肪组织。我们的结果表明,人ASC不仅充当体内脂肪生成的祖细胞,而且还可以长期诱导脂肪从头生成。
Adipose tissue-derived stem cells (ASCs), including preadipocytes, may play an important role in de novo adipogenesis and are expected to be a useful external source of cells for adipose tissue engineering. In this study, we examined in vivo adipogenesis up to 24 weeks after implantation, induced by human ASCs that were isolated from adipose tissues and expanded in vitro. ASCs proliferated in vitro in the presence of basic fibroblast growth factor (bFGF), and the number of cells increased by more than 1000-fold at the fourth passage. The ability to differentiate into mature adipocytes was maintained up to the third passage. We incorporated designated numbers of third-passage-expanded cells into a type I collagen scaffold and implanted them into the back of nude mice with or without controlled-release bFGF. After the implantation of 2 x 10(6) ASCs with controlled-release bFGF, the greatest cross-sectional surface area of adipose tissue in the scaffold was 1.19 mm(2) at 12 weeks and 2.14 mm(2) at 24 weeks. About 2 x 10(6) ASCs with controlled-release bFGF was the best condition for total adipogenesis. Immunohistochemical analysis with antihuman vimentin antibody showed that the area of human-origin adipose tissue was maximum in the group with 8 x 10(6) ASCs incorporated in a scaffold at both 12 and 24 weeks. The amount of human-origin adipose tissue increased in all groups with implanted ASCs from 12 to 24 weeks. Only trace of human-origin adipose tissue was observed in other groups implanted ASCs. Our results show that human ASCs not only function as progenitor cells for in vivo adipogenesis, but also induce de novo adipogenesis for long period.