In 2006, scientists in Japan rocked the biomedical world when their manipulations prompted mouse skin cells to revert to an embryonic-like state, from which they could potentially be turned into any type of body cell. The cells were dubbed induced pluripotent stem (iPS) cells, and the following year two groups successfully generated human iPS cells. These could obviate the need to destroy human embryos to generate stem cells, and may offer a new way to treat human diseases using a patient's own cells.

A group of scientists led by Juan Carlos Izpisúa Belmonte, a developmental biologist at the Salk Institute for Biological Studies in La Jolla, California, wasted no time in testing whether iPS cells could one day replace diseased cells in patients with Fanconi anaemia. This inherited blood disorder results from mutations in any of 13 known genes, the products of which maintain genetic stability. It can lead to bone-marrow failure, cancer and other problems. As a first step, the team has demonstrated that a patient's skin cells can be turned into disease-free blood-cell progenitors that could potentially be transplanted into humans.

Izpisúa Belmonte's previous research, which focused on understanding how some animals — such as frogs and salamanders — are able to regenerate limbs, fuelled his foray into human stem-cell research. To negotiate this new territory, he partnered with basic scientists and clinicians in Spain, Italy and California. “For someone with my background to help to produce this type of focused regenerative-medicine study speaks to the importance of collaboration in science,” he says.

The team's first task was to turn skin cells from a patient with Fanconi anaemia into iPS cells. The researchers used viruses to introduce four 'reprogramming' genes into the cells, but repeated efforts with the Fanconi anaemia cells didn't work. One team member pointed out that the cells might have too many abnormalities to be successfully reprogrammed. “We realized that we had to correct the genetic defects first,” says Izpisúa Belmonte. To do so, they used viral vectors to introduce corrected versions of two of the Fanconi anaemia genes into cells.

Once the genetic defects had been corrected, the group was able to generate iPS cells. Turning these cells into progenitors of healthy blood cells was relatively straightforward. However, it did take several attempts to work out the experimental details, because there was no well-established protocol. Eventually, though, the group succeeded — creating the first patient-specific, disease-corrected cells (see page 53).

“We cured a cell, but we haven't cured a patient,” says Izpisúa Belmonte, calling this work a “proof of principle”. One crucial hurdle remains. Introducing foreign genes — such as those used to reprogram skin cells — can cause tumours to form, a particularly troublesome side effect for the already tumour-prone individuals with Fanconi anaemia. “Before this technology can be brought into the clinic, we will have to be able to generate cells that do not produce tumours,” says Izpisúa Belmonte, “or find a way to readily kill any potentially tumorigenic cell before transplanting them into patients.”

But he remains cautiously optimistic that it can be done. “Just a few years ago, the ability to reprogram mature cells caused the entire community to change its perspective, so you never know where the science will lead,” he says.