Matsumoto Taro, Kano Koichiro, Kondo Daisuke, Fukuda Noboru, Iribe Yuji, Tanaka Nobuaki, Matsubara Yoshiyuki, Sakuma Takahiro, Satomi Aya, Otaki Munenori, Ryu Jyunnosuke, Mugishima Hideo
Division of Cell Regeneration and Transplantation, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo, Japan.
J Cell Physiol. 2008 Apr;215(1):210-22. doi: 10.1002/jcp.21304.
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 (PPARgamma), 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.
当成熟脂肪细胞采用一种称为悬滴培养的体外去分化策略时，这些成熟脂肪细胞可恢复为更原始的表型并获得细胞增殖能力。我们将这些细胞称为去分化脂肪（DFAT）细胞。在本研究中，我们检测了DFAT细胞的多向分化潜能。从18名供体的脂肪组织中获取的DFAT细胞呈现成纤维细胞样形态，并持续具有高增殖活性。流式细胞术分析显示，与脂肪来源的干/基质细胞（ASC）相比，DFAT细胞构成了一个高度均一的细胞群体，尽管DFAT细胞的细胞表面抗原谱与ASC非常相似。DFAT细胞失去了成熟脂肪细胞标志物基因的表达，但保留或获得了间充质谱系定向标志物基因如过氧化物酶体增殖物激活受体γ（PPARγ）、RUNX2和SOX9的表达。体外分化分析表明，在适当的培养条件下，DFAT细胞可分化为脂肪细胞、软骨细胞和成骨细胞。当皮下植入裸鼠时，DFAT细胞也形成了类骨质基质。此外，克隆扩增的猪DFAT细胞显示出分化为多种间充质细胞谱系的能力。这些结果表明，DFAT细胞代表了一种多能祖细胞。DFAT细胞易于获取和培养，这支持了它们在基于细胞的治疗中的潜在应用。
