Induced Pluripotent Stem Cells: Emerging Techniques for Nuclear Reprogramming

Division of Cardiology, Department of Medicine, Emory University School of Medicine, 1639 Pierce Drive, Atlanta, GA 30322, USA.
Antioxidants & Redox Signaling (Impact Factor: 7.41). 10/2011; 15(7):1799-820. DOI: 10.1089/ars.2010.3814
Source: PubMed


Introduction of four transcription factors, Oct3/4, Sox2, Klf4, and c-Myc, can successfully reprogram somatic cells into embryonic stem (ES)-like cells. These cells, which are referred to as induced pluripotent stem (iPS) cells, closely resemble embryonic stem cells in genomic, cell biologic, and phenotypic characteristics, and the creation of these special cells was a major triumph in cell biology. In contrast to pluripotent stem cells generated by somatic cell nuclear-transfer (SCNT) or ES cells derived from the inner cell mass (ICM) of the blastocyst, direct reprogramming provides a convenient and reliable means of generating pluripotent stem cells. iPS cells have already shown incredible potential for research and for therapeutic applications in regenerative medicine within just a few years of their discovery. In this review, current techniques of generating iPS cells and mechanisms of nuclear reprogramming are reviewed, and the potential for therapeutic applications is discussed.

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Available from: Ji Woong Han, Aug 14, 2014
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    • "This iPS, which is morphologically and characteristically close to ES, can be differentiated to various types of tissues and replenish host tissue loss in neurodegenerative and other diseases. Direct reprogramming of cells by iPS is more convenient and reliable than generation of pluripotent cells from ICM of blastocyst [10]. However, different studies have shown that iPS cells are not as superior as ES cells. "
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    ABSTRACT: During embryonic development pluripotency is progressively lost irreversibly by cell division, differentiation, migration and organ formation. Terminally differentiated cells do not generate other kinds of cells. Pluripotent stem cells are a great source of varying cell types that are used for tissue regeneration or repair of damaged tissue. The pluripotent stem cells can be derived from inner cell mass of blastocyte but its application is limited due to ethical concerns. The recent discovery of iPS with defined reprogramming factors has initiated a flurry of works on stem cell in various laboratories. The pluripotent cells can be derived from various differentiated adult cells as well as from adult stem cells by nuclear reprogramming, somatic cell nuclear transfer etc. In this review article, different aspects of nuclear reprogramming are discussed.
    Full-text · Article · Oct 2011
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    • "Inhibition of histone deacetylase or DNA methyltransferase with the use of epigenetic modifiers such as valproic acid and azacytidine, alters chromatin remodeling and increases the efficiency of standardized reprogramming protocols [22], [11]. Various combinations of reprogramming factors with concomitant small molecule treatment have been used for reprogramming of somatic cells to yield better quality iPS cells with more efficiency [23], [24]. Consequently, it is highly desirable to identify new conditions/small molecules that can promote reprogramming and/or replace certain factors. "
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    ABSTRACT: The current protocols for generation of induced pluripotent stem (iPS) cells involve genome integrating viral vectors which may induce tumorgenesis. The aim of this study was to develop and optimize a non-viral method without genetic manipulation for reprogramming of skeletal myoblasts (SMs) using small molecules. Methods and Results SMs from young male Oct3/4-GFP+ transgenic mouse were treated with DNA methyltransferase (DNMT) inhibitor, RG108. Two weeks later, GFP+ colonies of SM derived iPS cells (SiPS) expressing GFP and with morphological similarity of mouse embryonic stem (ESCs) were formed and propagated in vitro. SiPS were positive for alkaline phosphatase activity, expressed SSEA1, displayed ES cell specific pluripotency markers and formed teratoma in nude mice. Optimization of culture conditions for embryoid body (EBs) formation yielded spontaneously contracting EBs having morphological, molecular, and ultra-structural similarities with cardiomyocytes and expressed early and late cardiac markers. miR profiling showed abrogation of let-7 family and upregulation of ESCs specific miR-290-295 cluster thus indicating that SiPS were similar to ESCs in miR profile. Four weeks after transplantation into the immunocompetent mice model of acute myocardial infarction (n = 12 per group), extensive myogenesis was observed in SiPS transplanted hearts as compared to DMEM controls (n = 6 per group). A significant reduction in fibrosis and improvement in global heart function in the hearts transplanted with SiPS derived cardiac progenitor cells were observed. Conclusions Reprogramming of SMs by DNMT inhibitor is a simple, reproducible and efficient technique more likely to generate transgene integration-free iPS cells. Cardiac progenitors derived from iPS cells propagated extensively in the infarcted myocardium without tumorgenesis and improved cardiac function.
    Preview · Article · Aug 2011 · PLoS ONE
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    Full-text · Article · Mar 2011 · Antioxidants & Redox Signaling
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