Mature adipocyte-derived dedifferentiated fat cells exhibit multilineage potential
Mature adipocyte-derived dedifferentiated fat cells exhibit multilineage potential
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DOI：
10.1002/jcp.21304
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发表时间：
2008-04-01
影响因子：
5.6
通讯作者：
Mugishima, Hideo
中科院分区：
文献类型：
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作者：
Matsumoto, Taro;Kano, Koichiro;Mugishima, Hideo
当成熟的脂肪细胞接受体外去分化策略（称为天花板培养）时，这些成熟的脂肪细胞可以恢复到更原始的表型并获得细胞增殖能力。我们把这些细胞称为去分化脂肪（DFAT）细胞。在本研究中，我们研究了DFAT细胞的多系分化潜能。从18个供体脂肪组织中获得的DFAT细胞表现出成纤维细胞样形态和持续的高增殖活性。流式细胞术分析显示，尽管DFAT细胞的细胞表面抗原谱与ASCs非常相似，但与脂肪源性干细胞/基质细胞（ASCs）相比，DFAT细胞构成了一个高度均匀的细胞群。DFAT细胞失去了成熟脂肪细胞标记基因的表达，但保留或获得了间充质谱系标记基因的表达，如过氧化物酶体增殖物激活受体γ (PPAR γ)、RUNX2和SOX9。体外分化分析显示，在适当的培养条件下，DFAT细胞可以分化为脂肪细胞、软骨细胞和成骨细胞。裸鼠皮下植入DFAT细胞也可形成类骨基质。此外，克隆扩增的猪DFAT细胞显示出向多个间充质细胞系分化的能力。这些结果表明，DFAT细胞是一种多能祖细胞。DFAT细胞的易获得性和易于培养性支持了它们在细胞治疗中的潜在应用。
When mature adipocytes are subjected to an in vitro dedifferentiation strategy referred to as ceiling culture, these mature adipocytes can revert to a more primitive phenotype and gain cell proliferative ability. We refer to these cells as dedifferentiated fat (DFAT) cells. In the present study, we examined the multilineage differentiation potential of DFAT cells. DFAT cells obtained from adipose tissues of 18 donors exhibited a fibroblast-like morphology and sustained high proliferative activity. Flow cytometric analysis revealed that DFAT cells comprised a highly homogeneous cell population compared with that of adipose-derived stem/stromal cells (ASCs), although the cell-surface antigen profile of DFAT cells was very similar to that of ASCs. DFAT cells lost expression of mature adipocytes marker genes but retained or gained expression of mesenchymal lineage-committed marker genes such as peroxisome proliferator-activated receptor gamma (PPAR gamma), RUNX2, and SOX9. In vitro differentiation analysis revealed that DFAT cells could differentiate into adipocytes, chondrocytes, and osteoblasts under appropriate culture conditions. DFAT cells also formed osteoid matrix when implanted subcutaneously into nude mice. In addition, clonally expanded porcine DFAT cells showed the ability to differentiate into multiple mesenchymal cell lineages. These results indicate that DFAT cells represent a type of multipotent progenitor cell. The accessibility and ease of culture of DFAT cells support their potential application for cell-based therapies.