induced Pluripotent Stem cells: embryo-like stem cells from adult skin cells


 
    Stem cell researchers in Wisconsin (
James Thomson, who first isolated stem cells from 5-day-old human embryos in 1998) and Japan (Kyoto University's Shinya Yamanaka, who has led the recent effort to obtain mouse stem cells without embryos) report they have turned adult differentiated human skin cells into what are effectively embryonic stem cells (hES) without using embryos or women's eggs.  The technique is technically known as somatic cell dedifferentiation. Previously, the only source of totipotent stem cells to date has been from early embryonic cells. 
    
Thomson & Yamanaka used a new method of transfecting adult cells with genetically engineered viruses to transform them into embryo-like ones  (figure)In essence they took a cell that has become quite specialized, making skin in this case, and by changing its genetic environment, they took the cell and made it think it's back in the embryo and it has the full potential to make every cell in the body. The work with Human cells builds on a study published last year by Shinya Yamanaka of Kyoto University in Japan, which showed that mouse tail cells could be transformed into ES-like cells by inserting four genes (ScienceNOW, 3 July 2006 - Scientific American report). Those genes are normally switched off after embryonic cells differentiate into the various cell types. In June this year, Yamanaka and another group reported that the cells were truly pluripotent, meaning that they had the potential to grow into any tissue in the body (ScienceNOW, 6 June).

    Yamanaka and his colleagues used a retrovirus to transfect into adult cells the same four genes they had previously used to reprogram the mouse cells: OCT3/4, SOX2, KLF4, and c-MYC. These 4 genes code for transcription factors that favor an embryonic state. They transfected cells taken from the facial skin of a 36-year-old woman and from connective tissue from a 69-year-old man. Roughly one iPS cell line was produced for every 5000 cells the researchers treated using the technique, an efficiency that enabled them to produce several cell lines from each experiment. The iPS cells produced were indistinguishable from hES in morphology, proliferation, surface antigens, telomerase activity and gene expression.

     Thomson's team identified a list of 14 possible reprogramming genes and like Yamanaka's group, settled on four factors: OCT3 and SOX2 (also used by Yamanaka) and two different genes, NANOG and LIN28. The group reprogrammed cells from fetal skin and from the foreskin of a newborn boy. The researchers were able to transform about one in 10,000 cells, less than Yamanaka's technique achieved but still enough to create several cell lines from a single experiment.

     Although promising, both techniques share a downside. The retroviruses used to insert the genes have a downside because they cause tumors in tissues grown from the cells. It is expected that a virus-free methodology will be soon found. Thomson's and Yamanaka's reports were published Tuesday (11/20/07) in online editions of the journals Science and Cell, respectively