George Daley is exploring the potential of induced pluripotent cells.

In November 2007, two groups headed by James Thompson at the University of Wisconsin-Madison and Shinya Yamanaka at Kyoto University in Japan made headlines when they described methods to reprogramme adult human cells to a pluripotent state. These cells, called induced pluripotent stem (iPS) cells, are genetically modified by the integration of up to four DNA-transcription factors into the adult cell genome. Soon after, in December, George Daley, of Harvard Medical School in Boston, Massachusetts, and his colleagues also demonstrated iPS cells could be generated from a wide variety of adult cells. “For any patient we can use the technique and take a skin biopsy to establish a pluripotent cell,” says Daley. One of the most valuable aspects of the iPS-cell technology currently, he says, is the ability to perform disease modelling. And to take advantage of this, Daley and his colleagues are working on generating large numbers of disease specific iPS-cell lines.

Although an incredible step forward in stem-cell research, iPS cells are in fact at the beginning of a long road. “iPS cells as we make them today are riddled with viruses,” says Daley. He says that these viruses can be mutagenic and have the potential to activate oncogenes, so at the moment iPS cells remain a research tool and not a potential therapeutic agent. But the next step for iPS cells could move them closer to therapeutic applications. “One of the next big milestones will be making these cells without the use of viruses — leaving the cells in a genetically pristine state,” he says. Robert Lanza from Advanced Cell Technologies in Worcester, Massachusetts agrees and even sees routes to creating iPS cells without genetic modification. “You can potentially use fusion proteins or small molecules — there are many ways to skin the cat here.”

But even if iPS cells can be created without genetic modifications, the question that researchers are asking now is, do these cells really have the same properties and potentials as embryonic stem cells? “I am very excited about iPS cells but now we need to look very carefully at the properties of these cell lines,” says Martin Pera of the University of Southern California in Los Angeles. Pera says that these cells might differ in their abilities to differentiate in the same way that embryonic stem cells seem to. “If you have to make ten lines for each patient — is patient-specific therapy really realistic or will large banks of iPS cells that are tissue typed be required?” asks Pera.

Only time will tell in what directions iPS cells might be taken for basic research or for clinical applications. And while iPS-cell properties are being studied and new methods to derive these cells without genetic modifications are being created, human embryonic stem-cell research will continue. Pera says that this is the best way to proceed at the moment. “We need to move forward on both fronts.”

N.B.