A chemical platform for improved induction of human iPSCs.

Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA.
Nature Methods (Impact Factor: 23.57). 11/2009; 6(11):805-8. DOI: 10.1038/nmeth.1393
Source: PubMed

ABSTRACT The slow kinetics and low efficiency of reprogramming methods to generate human induced pluripotent stem cells (iPSCs) impose major limitations on their utility in biomedical applications. Here we describe a chemical approach that dramatically improves (200-fold) the efficiency of iPSC generation from human fibroblasts, within seven days of treatment. This will provide a basis for developing safer, more efficient, nonviral methods for reprogramming human somatic cells.

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    ABSTRACT: The breakthrough of reprogramming human somatic cells was achieved in 2006 by the work of Yamanaka and Takahashi. From this point, fibroblasts are the most commonly used primary somatic cell type for the generation of induced pluripotent stem cells (iPSCs). Various characteristics of fibroblasts supported their utilization for the groundbreaking experiments of iPSC generation. One major advantage is the high availability of fibroblasts which can be easily isolated from skin biopsies. Furthermore, their cultivation, propagation, and cryoconservation properties are uncomplicated with respect to nutritional requirements and viability in culture. However, the required skin biopsy remains an invasive approach, representing a major drawback for using fibroblasts as the starting material. More and more studies appeared over the last years, describing the reprogramming of other human somatic cell types. Cells isolated from blood samples or urine, as well as more unexpected cell types, like pancreatic islet beta cells, synovial cells, or mesenchymal stromal cells from wisdom teeth, show promising characteristics for a reprogramming strategy. Here, we want to highlight the advantages of keratinocytes from human plucked hair as a widely usable, noninvasive harvesting method for primary material in comparison with other commonly used cell types.
    Stem cells international. 01/2014; 2014:768391.
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    ABSTRACT: The reprogramming of differentiated cells into induced pluripotent stem cells (iPSCs) can be achieved by ectopic expression of defined transcription factors (Oct3/4, Sox2, Klf4 and c-Myc). However, to date, some iPSCs have been generated using viral vectors; thus, unexpected insertional mutagenesis in the target cells would be a potential risk. Here we report reprogramming of siPSCs (gene silencing-induced pluripotent stem cells) from mouse neonatal cardiomyocytes (CMs) by combining TGF-β signal inhibition and connexin43 (Cx43) silencing, and show that siPSCs show pluripotency in vitro and in vivo. Our novel non-insertional mutagenesis technique may provide a means for iPSC generation.
    Scientific Reports 12/2014; 4:7323. · 5.08 Impact Factor
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    ABSTRACT: The reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) by defined transcription factors has been a well-established technique and will provide an invaluable resource for regenerative medicine. However, the low reprogramming efficiency of human iPSC is still a limitation for clinical application. Here we showed that the reprogramming potential of human dental pulp cells (DPCs) obtained from immature teeth is much higher than those of mature teeth DPCs. Furthermore, immature teeth DPCs can be reprogrammed by OCT3/4 and SOX2, conversely these two factors are insufficient to convert mature teeth DPCs to pluripotent states. Using a gene expression profiles between these two DPC groups, we identified a new transcript factor, distal-less homeobox 4 (DLX4), which was highly expressed in immature teeth DPCs and significantly promoted human iPSC generation in combination with OCT3/4, SOX2, and KLF4. We further show that activation of TGF-β signaling suppresses the expression of DLX4 in DPCs and impairs the iPSC generation of DPCs. Our findings indicate that DLX4 can functionally replace c-MYC and supports efficient reprogramming of immature teeth DPCs.
    Scientific Reports 12/2014; 4:7283. · 5.08 Impact Factor

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