Awakened by cellular stress: isolation and characterization of a novel population of pluripotent stem cells derived from human adipose tissue.
Awakened by cellular stress: isolation and characterization of a novel population of pluripotent stem cells derived from human adipose tissue.
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DOI：
10.1371/journal.pone.0064752
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chazenbalk G
中科院分区：
文献类型：
--
作者：
Heneidi S;Simerman AA;Keller E;Singh P;Li X;Dumesic DA;Chazenbalk G
干细胞治疗的进展面临着重大的临床限制，特别是移植后细胞存活率低的挑战。移植微环境的敌对宿主因素，如缺氧、营养剥夺、促炎细胞因子和活性氧物质，均可导致不需要的分化或凋亡。在这份报告中，我们描述了一个新的人口的脂肪组织（AT）衍生的多能干细胞，称为多系分化应力持久（缪斯）细胞，这是分离使用严重的细胞应激条件下，包括长期暴露于蛋白水解酶胶原酶，血清剥夺，低温和缺氧的分离和表征。在这些条件下，分离高度纯化的Muse-AT细胞群而不使用细胞分选方法。Muse-AT细胞在悬浮液中生长为细胞球，使人联想到胚胎干细胞簇。Muse-AT细胞对多能性标志物SSEA 3、TR-1-60、Oct 3/4、Nanog和Sox 2呈阳性，并且可以自发分化成间充质、内胚层和外胚层细胞谱系，效率分别为23%、20%和22%。当使用特异性分化培养基时，Muse-AT细胞的分化效率大大提高（间充质细胞为82%，内胚层细胞为75%，外胚层细胞为78%）。当与脂肪干细胞（ASC）相比时，微阵列数据表明Sox 2、Oct 3/4和Rex 1的显著上调。Muse-AT还表现出与涉及细胞死亡和存活、胚胎发育、DNA复制和修复、细胞周期和与致癌性相关的潜在因子的基因下调相关的基因表达模式。基因表达分析表明，Muse-AT和ASC是间充质起源的;然而，Muse-AT也表达许多淋巴细胞和造血基因，如CCR 1和CXCL 2，编码参与干细胞归巢的趋化因子受体和配体。由于对严重的细胞应激具有高度抵抗力，Muse-AT细胞有可能对再生医学和基于细胞的治疗领域产生关键影响。
Advances in stem cell therapy face major clinical limitations, particularly challenged by low rates of post-transplant cell survival. Hostile host factors of the engraftment microenvironment such as hypoxia, nutrition deprivation, pro-inflammatory cytokines, and reactive oxygen species can each contribute to unwanted differentiation or apoptosis. In this report, we describe the isolation and characterization of a new population of adipose tissue (AT) derived pluripotent stem cells, termed Multilineage Differentiating Stress-Enduring (Muse) Cells, which are isolated using severe cellular stress conditions, including long-term exposure to the proteolytic enzyme collagenase, serum deprivation, low temperatures and hypoxia. Under these conditions, a highly purified population of Muse-AT cells is isolated without the utilization of cell sorting methods. Muse-AT cells grow in suspension as cell spheres reminiscent of embryonic stem cell clusters. Muse-AT cells are positive for the pluripotency markers SSEA3, TR-1-60, Oct3/4, Nanog and Sox2, and can spontaneously differentiate into mesenchymal, endodermal and ectodermal cell lineages with an efficiency of 23%, 20% and 22%, respectively. When using specific differentiation media, differentiation efficiency is greatly enhanced in Muse-AT cells (82% for mesenchymal, 75% for endodermal and 78% for ectodermal). When compared to adipose stem cells (ASCs), microarray data indicate a substantial up-regulation of Sox2, Oct3/4, and Rex1. Muse-ATs also exhibit gene expression patterns associated with the down-regulation of genes involved in cell death and survival, embryonic development, DNA replication and repair, cell cycle and potential factors related to oncogenecity. Gene expression analysis indicates that Muse-ATs and ASCs are mesenchymal in origin; however, Muse-ATs also express numerous lymphocytic and hematopoietic genes, such as CCR1 and CXCL2, encoding chemokine receptors and ligands involved in stem cell homing. Being highly resistant to severe cellular stress, Muse-AT cells have the potential to make a critical impact on the field of regenerative medicine and cell-based therapy.
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影响因子：
5.2
作者：
Dayem AA;Choi HY;Kim JH;Cho SG
通讯作者：
Cho SG
影响因子：
3.7
作者：
Chazenbalk G;Bertolotto C;Heneidi S;Jumabay M;Trivax B;Aronowitz J;Yoshimura K;Simmons CF;Dumesic DA;Azziz R
通讯作者：
Azziz R
影响因子：
64.5
作者：
Acharyya S;Oskarsson T;Vanharanta S;Malladi S;Kim J;Morris PG;Manova-Todorova K;Leversha M;Hogg N;Seshan VE;Norton L;Brogi E;Massagué J
通讯作者：
Massagué J
影响因子：
3.9
作者：
Beier, Justus P.;Bitto, Franz F.;Kneser, Ulrich
通讯作者：
Kneser, Ulrich
影响因子：
37.8
作者：
Hofmann, M;Wollert, KC;Drexler, H
通讯作者：
Drexler, H