The bogey of making cells that behave like embryonic stem cells has been genetic engineering: so far, reprogramming human cells has required permanent genetic modification, a fact that raises worries of increased cancer risk and unpredictability.
Three prominent papers this week describe reprogramming cells without permanent genetic baggage. They use genetic material that gets into cells, reprograms them, and snips themselves out.
Work published Sunday in Nature dispensed with viruses and instead engineered a transposon called piggyBac to take itself in and out of the cells. That work was led by Andreas Nagy, of Mount Sinai Hospital in Toronto, Canada, and Keisuke Kaji, of the University of Edinburgh, UK. (See Virus free pluripotency for human cells ) On Thursday, a paper by MIT’s Rudolf Jaenisch published in Cell took the cells much further (See Test tube disease models one step closer.) They reprogrammed cells from five patients with Parkinson’s disease and then showed that these reprogrammed cells could be differentiated into neurons. They use an engineered virus that snips out the integrated reprogramming genes once the cells have transformed. Though it leaves behind some remnants of the virus, it removes potentially dangerous genes. Perhaps more importantly, the iPS cells from which the reprogramming genes have been removed behave more like embryonic stem cells.
As Nature’s Erika Check Hayden reports: “While 48 genes were expressed differently between the factor-free iPS cells and the embryonic stem cells, 271 genes differed between the factor-free iPS cells and the iPS cells that retained the factors.”
Though the work is exciting, the race is still on for new techniques to derive iPS cells. The holy grail is to transform the cells without using DNA at all, presumably by adding small molecules and proteins that cause adult cells to reactivate their own, silenced version of pluripotency genes.
Though the cells appear to be very, very similar in their undifferentiated state, and mouse iPS cells can contribute to all tissues in a chimeric mouse, researchers warn that the mechanism by which cells are reprogrammed is not fully understood. The next steps are to study cells differentiated from both ES and iPS cells to see which would be best for cell therapies and drug screening.
Integration-free iPS cells describes other DNA-based techniques to reprogram cells without permant genetic modification.
Cells reprogrammed using only one gene describes a recent paper using proteins and small molecules to reprogram cells and includes links to several related research highlights.
For lay coverage of the self-excising reprogramming factors, see the LA Times , which covers all three papers, the New York Times, which covers the Jaenisch paper and has a nice description of the Jaenisch construct, and the Washington Post, which covers the transposon papers and how techniques to make pluripotent stem cells without embryos might impact political battles over the funding of ES cell work.