Ogura Fumitaka, Wakao Shohei, Kuroda Yasumasa, Tsuchiyama Kenichiro, Bagheri Mozhdeh, Heneidi Saleh, Chazenbalk Gregorio, Aiba Setsuya, Dezawa Mari
1 Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine , Sendai, Japan .
Stem Cells Dev. 2014 Apr 1;23(7):717-28. doi: 10.1089/scd.2013.0473. Epub 2014 Jan 17.
In this study, we demonstrate that a small population of pluripotent stem cells, termed adipose multilineage-differentiating stress-enduring (adipose-Muse) cells, exist in adult human adipose tissue and adipose-derived mesenchymal stem cells (adipose-MSCs). They can be identified as cells positive for both MSC markers (CD105 and CD90) and human pluripotent stem cell marker SSEA-3. They intrinsically retain lineage plasticity and the ability to self-renew. They spontaneously generate cells representative of all three germ layers from a single cell and successfully differentiate into targeted cells by cytokine induction. Cells other than adipose-Muse cells exist in adipose-MSCs, however, do not exhibit these properties and are unable to cross the boundaries from mesodermal to ectodermal or endodermal lineages even under cytokine inductions. Importantly, adipose-Muse cells demonstrate low telomerase activity and transplants do not promote teratogenesis in vivo. When compared with bone marrow (BM)- and dermal-Muse cells, adipose-Muse cells have the tendency to exhibit higher expression in mesodermal lineage markers, while BM- and dermal-Muse cells were generally higher in those of ectodermal and endodermal lineages. Adipose-Muse cells distinguish themselves as both easily obtainable and versatile in their capacity for differentiation, while low telomerase activity and lack of teratoma formation make these cells a practical cell source for potential stem cell therapies. Further, they will promote the effectiveness of currently performed adipose-MSC transplantation, particularly for ectodermal and endodermal tissues where transplanted cells need to differentiate across the lineage from mesodermal to ectodermal or endodermal in order to replenish lost cells for tissue repair.
在本研究中,我们证明在成人脂肪组织和脂肪来源的间充质干细胞(脂肪间充质干细胞)中存在一小部分多能干细胞,称为脂肪多谱系分化应激耐受(脂肪-Muse)细胞。它们可被鉴定为同时表达间充质干细胞标志物(CD105和CD90)和人类多能干细胞标志物SSEA-3的细胞。它们内在地保留了谱系可塑性和自我更新能力。它们能从单个细胞自发产生代表所有三个胚层的细胞,并通过细胞因子诱导成功分化为目标细胞。然而,脂肪间充质干细胞中除脂肪-Muse细胞外的其他细胞不具备这些特性,即使在细胞因子诱导下也无法跨越从中胚层到外胚层或内胚层谱系的界限。重要的是,脂肪-Muse细胞表现出低端粒酶活性,并且移植在体内不会促进畸胎瘤形成。与骨髓(BM)-和真皮-Muse细胞相比,脂肪-Muse细胞在中胚层谱系标志物中往往表现出更高的表达,而BM-和真皮-Muse细胞在外胚层和内胚层谱系标志物中通常更高。脂肪-Muse细胞的优势在于易于获取且分化能力多样,而低端粒酶活性和不形成畸胎瘤使这些细胞成为潜在干细胞治疗的实用细胞来源。此外,它们将提高目前进行的脂肪间充质干细胞移植的有效性,特别是对于外胚层和内胚层组织,在这些组织中,移植细胞需要从中胚层跨越谱系分化为外胚层或内胚层,以补充丢失的细胞用于组织修复。