Chang Wing Y, Lavoie Jessie R, Kwon Sarah Y, Chen Zhaoyi, Manias Janet L, Behbahani John, Ling Vicki, Kandel Rita A, Stewart Duncan J, Stanford William L
Sprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada.
Stem Cell Res. 2013 Mar;10(2):195-202. doi: 10.1016/j.scr.2012.11.006. Epub 2012 Dec 3.
Induced-pluripotent stem cells (iPSCs) are a potential alternative cell source in regenerative medicine, which includes the use of differentiated iPSCs for cell therapies to treat coronary artery and/or peripheral arterial diseases. Late-outgrowth endothelial progenitor cells (late-EPCs) are a unique primary cell present in peripheral blood that exhibit high proliferative capacity, are being used in a wide variety of clinical trials, and have the ability to differentiate into mature endothelial cells. The objective of this study was to reprogram peripheral blood-derived late-EPCs to a pluripotent state under feeder-free and defined culture conditions. Late-EPCs that were retrovirally transduced with OCT4, SOX2, KLF4, c-MYC, and iPSC colonies were derived in feeder-free and defined media conditions. EPC-iPSCs expressed pluripotent markers, were capable of differentiating to cells from all three germ-layers, and retained a normal karyotype. Transcriptome analyses demonstrated that EPC-iPSCs exhibit a global gene expression profile similar to human embryonic stem cells (hESCs). We have generated iPSCs from late-EPCs under feeder-free conditions. Thus, peripheral blood-derived late-outgrowth EPCs represent an alternative cell source for generating iPSCs.
诱导多能干细胞(iPSC)是再生医学中一种潜在的替代细胞来源,其中包括使用分化的iPSC进行细胞治疗,以治疗冠状动脉和/或外周动脉疾病。晚期内皮祖细胞(late-EPC)是外周血中存在的一种独特的原代细胞,具有高增殖能力,正在广泛用于各种临床试验,并且能够分化为成熟的内皮细胞。本研究的目的是在无饲养层和明确的培养条件下,将外周血来源的晚期内皮祖细胞重编程为多能状态。用OCT4、SOX2、KLF4、c-MYC进行逆转录病毒转导的晚期内皮祖细胞和iPSC集落是在无饲养层和明确的培养基条件下获得的。EPC-iPSC表达多能性标志物,能够分化为来自所有三个胚层的细胞,并保持正常的核型。转录组分析表明,EPC-iPSC表现出与人类胚胎干细胞(hESC)相似的整体基因表达谱。我们在无饲养层条件下从晚期内皮祖细胞生成了iPSC。因此,外周血来源的晚期内皮祖细胞代表了一种生成iPSC的替代细胞来源。