Generation of Rat and Human Induced Pluripotent Stem Cells by Combining Genetic Reprogramming and Chemical Inhibitors

Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Cell stem cell (Impact Factor: 22.27). 04/2009; 4(1):16-9. DOI: 10.1016/j.stem.2008.11.014
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Available from: Saiyong Zhu, Jun 13, 2014
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    • "However, cultivation of stem cells in the presence of 2i (two small molecules: CHIR99021 and PD0325901) and LIF can induce a naïve state in mouse pluripotent stem cells (Hanna et al., 2009; Ying et al., 2008). Moreover, several groups recently generated mESC-like hiPSCs by applying the naïve culture conditions after inducing with reprogramming factors; however, such cell lines lack the phenotypic stability that distinguishes bona fide mESCs/iPSCs (Hanna et al., 2010; Li et al., 2009). In this study, we did not detect the expression of pluripotency markers in several of the hiPSC lines when cultivating the cells in the presence of 2i and LIF, and absence of reprogramming factors. "
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    ABSTRACT: In mice, leukemia inhibitory factor (LIF)-dependent primitive neural stem cells (NSCs) have a higher neurogenic potential than bFGF-dependent definitive NSCs. Therefore, expandable primitive NSCs are required for research and for the development of therapeutic strategies for neurological diseases. There is a dearth of suitable techniques for the generation of human long-term expandable primitive NSCs. Here, we have described a method for the conversion of human fibroblasts to LIF-dependent primitive NSCs using a strategy based on techniques for the generation of induced pluripotent stem cells (iPSCs). These LIF-dependent induced NSCs (LD-iNSCs) can be expanded for >100 passages. Long-term cultured LD-iNSCs demonstrated multipotent neural differentiation potential and could generate motor neurons and dopaminergic neurons, as well as astrocytes and oligodendrocytes, indicating a high level of plasticity. Furthermore, LD-iNSCs easily reverted to human iPSCs, indicating that LD-iNSCs are in an intermediate iPSC state. This method may facilitate the generation of patient-specific human neurons for studies and treatment of neurodegenerative diseases.
    Preview · Article · Oct 2015 · Biology Open
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    • "Human or non-human primate PSCs with some features of naïve pluripotency have been derived by the conversion of conventional hESCs or induced PSCs (iPSCs) in vitro, through reprogramming of somatic cells to a pluripotent state or by direct derivation from the embryo (Tables 2 and 3) (Buecker et al., 2010; Chan et al., 2013; Fang et al., 2014; Gafni et al., 2013; Hanna et al., 2010; Li et al., 2009; Takashima et al., 2014; Theunissen et al., 2014; Valamehr et al., 2014; Ware et al., 2014, Wang et al., 2014). Early studies used exogenous transgenes to trigger the conversion from primed to naïve pluripotency and, in some cases, to stabilise and maintain the naïve state. "
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    ABSTRACT: In the mouse, naïve pluripotent stem cells (PSCs) are thought to represent the cell culture equivalent of the late epiblast in the pre-implantation embryo, with which they share a unique defining set of features. Recent studies have focused on the identification and propagation of a similar cell state in human. Although the capture of an exact human equivalent of the mouse naïve PSC remains an elusive goal, comparative studies spurred on by this quest are lighting the path to a deeper understanding of pluripotent state regulation in early mammalian development.
    Full-text · Article · Sep 2015 · Development
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    • "Chenxia Hu, Lanjuan Li molecules that affect methylation or acetylation, mimic the Wnt-signaling pathway, or modulate the TGF-b pathway (Li et al., 2009). These methods raised few ethical concerns because of their derivation from somatic cells and, thus, are powerful tools for studying basic developmental biology. "
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    ABSTRACT: Various liver diseases result in terminal hepatic failure, and liver transplantation, cell transplantation and artificial liver support systems are emerging as effective therapies for severe hepatic disease. However, all of these treatments are limited by organ or cell resources, so developing a sufficient number of functional hepatocytes for liver regeneration is a priority. Liver regeneration is a complex process regulated by growth factors (GFs), cytokines, transcription factors (TFs), hormones, oxidative stress products, metabolic networks, and microRNA. It is well-known that the function of isolated primary hepatocytes is hard to maintain; when cultured in vitro, these cells readily undergo dedifferentiation, causing them to lose hepatocyte function. For this reason, most studies focus on inducing stem cells, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), hepatic progenitor cells (HPCs), and mesenchymal stem cells (MSCs), to differentiate into hepatocyte-like cells (HLCs) in vitro. In this review, we mainly focus on the nature of the liver regeneration process and discuss how to maintain and enhance in vitro hepatic function of isolated primary hepatocytes or stem cell-derived HLCs for liver regeneration. In this way, hepatocytes or HLCs may be applied for clinical use for the treatment of terminal liver diseases and may prolong the survival time of patients in the near future.
    Full-text · Article · Jun 2015 · Protein & Cell
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