In vivo dedifferentiation of adult adipose cells.
In vivo dedifferentiation of adult adipose cells.
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成体脂肪细胞的体内去分化
DOI：
10.1371/journal.pone.0125254
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Gao J
中科院分区：
文献类型：
--
作者：
Liao Y;Zeng Z;Lu F;Dong Z;Chang Q;Gao J
脂肪细胞可以在体外脱分化为成纤维细胞样细胞，从而获得增殖和多能能力，参与各种器官和组织的修复。去分化是在生理还是病理条件下发生的尚不清楚。方法将组织扩张器置于大鼠腹股沟脂肪垫下，通过注射水逐渐扩张。在不同时间点采集样本，进行形态学、组织学、细胞学、超微结构和基因表达分析。在单独的实验中，将纯化的绿色荧光蛋白+脂肪细胞移植到C57小鼠体内，并在不同的时间点收集。采用生物发光显像和全载染色对移植脂肪细胞进行评价。结果膨胀后的脂肪垫明显薄于未处理的对侧脂肪垫。它的质地也更坚硬，附着的血管也更多。苏木精和伊红染色及透射电镜显示，扩大后的脂肪垫内单眼脂肪细胞减少，细胞形态发生改变，脂质含量明显减少。免疫组织化学显示，扩大的脂肪垫含有增加数量的增殖细胞，这可能来自脂肪细胞。取出组织扩张器后，观察到许多小脂肪细胞。生物发光成像显示，部分脂肪细胞移植到缺血-缺氧环境后存活。全载染色显示，存活的脂肪细胞经历了类似于体外脂肪细胞去分化的过程。单眼脂肪细胞变成多室脂肪细胞，然后变成成纤维细胞样细胞。结论成熟脂肪细胞在体内可能具有去分化的能力，这可能是一种脂肪组织的自我修复机制。脂肪细胞去分化为干细胞样细胞的能力也可能在许多组织的再生中发挥更普遍的作用，特别是在脂肪移植中。
Introduction Adipocytes can dedifferentiate into fibroblast-like cells in vitro and thereby acquire proliferation and multipotent capacities to participate in the repair of various organs and tissues. Whether dedifferentiation occurs under physiological or pathological conditions in vivo is unknown. Methods A tissue expander was placed under the inguinal fat pads of rats and gradually expanded by injection of water. Samples were collected at various time points, and morphological, histological, cytological, ultrastructural, and gene expression analyses were conducted. In a separate experiment, purified green fluorescent protein+ adipocytes were transplanted into C57 mice and collected at various time points. The transplanted adipocytes were assessed by bioluminescence imaging and whole-mount staining. Results The expanded fat pad was obviously thinner than the untreated fat pad on the opposite side. It was also tougher in texture and with more blood vessels attached. Hematoxylin and eosin staining and transmission electron microscopy indicated there were fewer monolocular adipocytes in the expanded fat pad and the morphology of these cells was altered, most notably their lipid content was discarded. Immunohistochemistry showed that the expanded fat pad contained an increased number of proliferative cells, which may have been derived from adipocytes. Following removal of the tissue expander, many small adipocytes were observed. Bioluminescence imaging suggested that some adipocytes survived when transplanted into an ischemic-hypoxic environment. Whole-mount staining revealed that surviving adipocytes underwent a process similar to adipocyte dedifferentiation in vitro. Monolocular adipocytes became multilocular adipocytes and then fibroblast-like cells. Conclusions Mature adipocytes may be able to dedifferentiate in vivo, and this may be an adipose tissue self-repair mechanism. The capacity of adipocytes to dedifferentiate into stem cell-like cells may also have a more general role in the regeneration of many tissues, notably in fat grafting.
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