Induction of pluripotent stem cells from adult somatic cells by protein-based reprogramming without genetic manipulation

Cho, Hyun Jai; Lee, Choon Soo; Kwon, Yoo Wook; Paek, Jae Seung; Lee, Sun Hee; Hur, Jin; Lee, Eun Ju; Roh, Tae-Young; Chu, In Sun; Leem, Sun Hee; Kim, Youngsoo; Kang, Hyun–Jae; Park, Young Bae; Kim, Hyo Soo

doi:10.1182/blood-2010-02-269589

Cited by 218 publications

(210 citation statements)

References 43 publications

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“…Optimizing delivery method of the transcription factors has been an attractive strategy to combat this inefficiency. Recent efforts have involved using non-integrating episomal plasmids [3] and viruses [40,41], the use of cell membrane-penetrating proteins [42][43][44] and the direct transfection of RNA [45]. Though some of these methods have produced poorer efficiencies than conventional reprogramming with retroviral delivery, they represent a step closer to clinical application, considering that each random integration event of a retrovirus is a potential genomic hazard.…”

Section: (Not) All Roads Lead To Romementioning

confidence: 99%

Reprogramming to pluripotency: stepwise resetting of the epigenetic landscape

2011

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In 2006, the "wall came down" that limited the experimental conversion of differentiated cells into the pluripotent state. In a landmark report, Shinya Yamanaka's group described that a handful of transcription factors (Oct4, Sox2, Klf4 and c-Myc) can convert a differentiated cell back to pluripotency over the course of a few weeks, thus reprograming them into induced pluripotent stem (iPS) cells. The birth of iPS cells started off a rush among researchers to increase the efficiency of the reprogramming process, to reveal the underlying mechanistic events, and allowed the generation of patient-and disease-specific human iPS cells, which have the potential to be converted into relevant specialized cell types for replacement therapies and disease modeling. This review addresses the steps involved in resetting the epigenetic landscape during reprogramming. Apparently, defined events occur during the course of the reprogramming process. Immediately, upon expression of the reprogramming factors, some cells start to divide faster and quickly begin to lose their differentiated cell characteristics with robust downregulation of somatic genes. Only a subset of cells continue to upregulate the embryonic expression program, and finally, pluripotency genes are upregulated establishing an embryonic stem cell-like transcriptome and epigenome with pluripotent capabilities. Understanding reprogramming to pluripotency will inform mechanistic studies of lineage switching, in which differentiated cells from one lineage can be directly reprogrammed into another without going through a pluripotent intermediate.

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Section: (Not) All Roads Lead To Romementioning

confidence: 99%

Reprogramming to pluripotency: stepwise resetting of the epigenetic landscape

2011

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“…Subsequently, another protein-based reprogramming approach adopted a certain group of embryonic stem cell-derived extract proteins, rather than DNA or RNA, to fully reprogram adult fibroblasts. 9 Recently, Hou et al transformed mouse somatic cells to the pluripotent state using only small-molecule compounds, providing another convenient pathway to generate iPSCs without genetic intervention. 10 Encouragingly, Israeli scientists 11 uncovered the crucial molecular hurdle in the reprogramming process-Mbd3, a core member of the Mbd3/nucleosome remodeling and deacetylation repressor.…”

Section: Advances In Ipsc Generation Methodsmentioning

confidence: 99%

Induced pluripotent stem cell (iPSCs) and their application in immunotherapy

2013

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The ever-improving technology to generate induced pluripotent stem cells (iPSCs) has increased their potential use as novel candidates for disease modeling, drug screening, regenerative medicine and cell therapy. Indeed, iPSCs offer extensive capacity for self-renewal without the ethical concerns faced by embryonic stem cells (ESCs). With respect to potential applications in the immune system, many studies provide evidence to support that there are exclusive advantages to using iPSCs over other systems. Both hematopoietic stem cells and several types of mature immune cells have successfully been reprogrammed to iPSCs and vice versa, paving a path toward our ability to effectively model patient-specific diseases and provide potentially alternative cell sources for transfusion medicine. Despite these potential advances, some limitations regarding the use of iPSCs in the clinic still remain, including the immunogenicity of iPSCs and their derivatives, which is currently under debate in the field. In this review, we mainly focus on discussing the recent progress being made in the latest differentiation methods and clinical implications of iPSCs with respect to the immune system. Additionally, current issues regarding the clinical application of iPSCs are addressed, especially the controversy surrounding immunogenicity, along with various other perspectives.

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“…Second, the early cellular reprogramming efforts were extremely inefficient, with only .0006 to 0.02% of transduced cells becoming iPS cells, [9,10,29]. Subsequent refinements, such as the plasmid-based, protein-based and modified RNA-based strategies, have led to successful virus-free, integration-free methods for cellular reprogramming [30][31][32][33]. Despite these successes, reprogramming remains a largely mysterious and inefficient process.…”

Section: B Small Molecules For Cellular Reprogrammingmentioning

confidence: 99%