Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells

Song, Zhihua; Cai, Jun; Liu, Yanxia; Zhao, Dongxin; Yong, Jun; Duo, Shuguang; Song, Xiaoyu; Guo, Yiduo; Zhao, Yang; Han, Qin; Yin, Xiaolei; Wu, Chen; Che, Jie; Lu, Shichun; Ding, Mei; Deng, Hongkui

doi:10.1038/cr.2009.107

Cited by 442 publications

(387 citation statements)

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“…Using previously established protocols, we differentiated hESCs and hiPSCs into derivatives representing all three embryonic germ layers: neural progenitor cells (NPCs) (ectoderm) [18], hepatocytes (endoderm) [20], and fibroblasts (FBs) (mesoderm). In our studies, the efficiency of derivation of various cell types from PSCs (including hESCs and FB-derived hiPSCs) was highly variable amongst various lines and across multiple experiments (data not shown and Karumbayaram et al [18]).…”

Section: Hesc and Hipsc Lines Are Capable Of Generating Derivatives Rmentioning

confidence: 99%

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Defining the nature of human pluripotent stem cell progeny

et al. 2011

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While it is clear that human pluripotent stem cells (hPSCs) can differentiate to generate a panoply of various cell types, it is unknown how closely in vitro development mirrors that which occurs in vivo. To determine whether human embryonic stem cells (hESCs) and human-induced pluripotent stem cells (hiPSCs) make equivalent progeny, and whether either makes cells that are analogous to tissue-derived cells, we performed comprehensive transcriptome profiling of purified PSC derivatives and their tissue-derived counterparts. Expression profiling demonstrated that hESCs and hiPSCs make nearly identical progeny for the neural, hepatic, and mesenchymal lineages, and an absence of re-expression from exogenous reprogramming factors in hiPSC progeny. However, when compared to a tissuederived counterpart, the progeny of both hESCs and hiPSCs maintained expression of a subset of genes normally associated with early mammalian development, regardless of the type of cell generated. While pluripotent genes (OCT4, SOX2, REX1, and NANOG) appeared to be silenced immediately upon differentiation from hPSCs, genes normally unique to early embryos (LIN28A, LIN28B, DPPA4, and others) were not fully silenced in hPSC derivatives. These data and evidence from expression patterns in early human fetal tissue (3-16 weeks of development) suggest that the differentiated progeny of hPSCs are reflective of very early human development (< 6 weeks). These findings provide support for the idea that hPSCs can serve as useful in vitro models of early human development, but also raise important issues for disease modeling and the clinical application of hPSC derivatives.

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Section: Hesc and Hipsc Lines Are Capable Of Generating Derivatives Rmentioning

confidence: 99%

“…[16][17][18][19][20][21]. While it is clear that hiPSCs are capable of generating similar cell types as hESCs as determined by expression of a select number of markers, it remains to be seen if, on a global level, these derivatives are truly analogous.…”

Section: Introductionmentioning

confidence: 99%

Defining the nature of human pluripotent stem cell progeny

et al. 2011

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“…Song et al (2009) described the first successful hepatic differentiation of human iPSC, closely followed by several other reports (Liu et al, 2010;Rashid et al, 2010;Si-Tayeb et al, 2010b;Sullivan et al, 2010). Similarly to the strategies developed in ESC differentiation, most reported studies of directed hepatic differentiation of human iPSC adopt multi-step protocols to mimic the liver embryogenesis by sequentially adding endodermal and hepatic inductive cytokines and small molecules.…”

Section: Introductionmentioning

confidence: 99%

Human induced pluripotent stem cells derived hepatocytes: rising promise for disease modeling, drug development and cell therapy

Liu

Belmonte

2012

Protein Cell

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Recent advances in the study of human hepatocytes derived from induced pluripotent stem cells (iPSC) represent new promises for liver disease study and drug discovery. Human hepatocytes or hepatocyte-like cells differentiated from iPSC recapitulate many functional properties of primary human hepatocytes and have been demonstrated as a powerful and efficient tool to model human liver metabolic diseases and facilitate drug development process. In this review, we summarize the recent progress in this field and discuss the future perspective of the application of human iPSC derived hepatocytes.

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“…For instance, iPS cells had been engineered to differentiate into liver hepatocytes and pancreatic endocrine (Cai et al 2007;D'Amour et al 2006;Song et al 2009;Zhang et al 2009). Moreover, a recent study reported the successful directed differentiation of human iPS cells into functional intestinal tissue in vitro by manipulating a temporal series of growth factors (Spence et al 2011).…”

Section: The Evolving Concept Of the Cancer Stem Cell Modelmentioning

confidence: 99%