Stem cells cruise to clinic

Induced pluripotent stem cells could soon be used in human trials in Japan.

Kathrin Plath lab, Univ. Calif. Los Angeles/CIRM

In the seven years since their discovery, induced pluripotent stem (iPS) cells have transformed basic research and won a Nobel prize. Now, a Japanese study is about to test the medical potential of these cells for the first time. Made by reprogramming adult cells into an embryo-like state that can form any cell type in the body, the cells will be transplanted into patients who have a debilitating eye disease.

Masayo Takahashi, an ophthalmologist at the RIKEN Center for Developmental Biology in Kobe, Japan, plans to submit her application for the study to the Japanese health ministry next month, and could be recruiting patients as early as September. Stem-cell researchers around the world hope that if the trial goes forward, it will allay some of the safety concerns over medical use of the cells. And the Japanese government hopes that its efforts to speed iPS cells to the clinic by generously funding such work will be vindicated (see Nature 493, 465; 2013).

The entire field is very dependent on this group and the Japanese regulatory agencies to ensure that preclinical evidence for safety and efficacy is very strong, says Martin Pera, a stem-cell expert at the University of Melbourne in Australia.

Takahashi, who has been studying the potential of iPS cells to rebuild diseased tissue for more than a decade, hopes to treat around six people who have severe age-related macular degeneration, a common cause of blindness that affects at least 1% of people aged over50. The form of the disease that Takahashi will treat occurs when blood vessels invade the retina, destroying the retinal pigment epithelium that supports the light-sensitive photoreceptors. This form can be treated with drugs that block the growth of new blood vessels, but these often have to be injected repeatedly into the eye.

Takahashi will take a peppercorn-size skin sample from the upper arm and add proteins that reprogram the cells into iPS cells. Other factors will transform the iPS cells into retinal cells. Then a small sheet of cells will be placed under the damaged area of the retina, where, if things go well, the cells will grow and repair the pigment epithelium.

The researchers hope to see the transplants slow or halt the disease, but their main goal is to show that the cells are safe. One concern is that the reprogrammed cells will trigger an immune reaction as has been seen in mice (T.Zhao etal. Nature 474, 212215; 2011). But that concern has faded after a recent study suggested that iPS cells did not provoke an immune reaction after all (see R. Araki et al. Nature 494, 100104; 2013 and Nature 493,145; 2013). Immune compatibility seems to be as expected, so I am not so concerned about that issue, says stem-cell expert George Daley of Harvard Medical School in Boston, Massachusetts.

A bigger worry is that the reprogrammed cells might multiply uncontrollably and form tumours instead of healthy tissue. But Pera and Daley are reassured by the pre-clinical data that Takahashi has presented at conferences. Takahashi says that these results, submitted for publication, show that her iPS cells do not form tumours in mice and are safe in non-human primates.

Pera adds that the procedure to treat macular degeneration requires just a few stem cells, reducing the chances that a tumour will form. Also, any tumours would be relatively easy to remove because the eye is more accessible than some organs.

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Stem cells cruise to clinic