Stem-cell pioneer banks on future therapies

Shinya Yamanaka aims to produce cell lines from fetal blood cells.

M. Naka/Aflo/Newscom

Progress toward stem-cell therapies has been frustratingly slow, delayed by research challenges, ethical and legal barriers and corporate jitters. Now, stem-cell pioneer Shinya Yamanaka of Kyoto University in Japan plans to jump-start the field by building up a bank of stem cells for therapeutic use. The bank would store dozens of lines of induced pluripotent stem (iPS) cells, putting Japan in an unfamiliar position: at the forefront of efforts to introduce a pioneering biomedical technology.

A long-held dream of Yamanakas, the iPS Cell Stock project received a boost last month, when a Japanese health-ministry committee decided to allow the creation of cell lines from the thousands of samples of fetal umbilical-cord blood held around the country. Yamanakas plan to store the cells for use in medicine is a bold move, says George Daley, a stem-cell biologist at Harvard Medical School in Boston, Massachusetts. But some researchers question whether iPS cells are ready for the clinic.

Yamanaka was the first researcher to show, in 2006, that mature mouse skin cells could be prodded into reverting to stem cells1 capable of forming all bodily tissues. The experiment, which he repeated2 with human cells in 2007, could bypass ethical issues associated with stem cells derived from embryos, and the cells could be tailor-made to match each patient, thereby avoiding rejection by the immune system.

Japan is pumping tens of millions of dollars every year into eight long-term projects to translate iPS cell therapies to the clinic, including a US$2.5-million-per-year effort to relieve Parkinsons disease at Kyoto Universitys Center for iPS Cell Research and Application (CiRA), which Yamanaka directs. That programme is at least three years away from clinical trials. The first human clinical trials using iPS cells, an effort to repair diseased retinas, are planned for next year at the RIKEN Center for Developmental Biology in Kobe.

Those trials will not use cells from Yamanakas Stock. But if they or any other iPS cell trials succeed, demand for the cells will explode, creating a supply challenge. Deriving and testing iPS cells tailored to individual patients could take six months for each cell line and cost tens of thousands of dollars.

Yamanakas plan is to create, by 2020, a standard array of 75 iPS cell lines that are a good enough match to be tolerated by 80% of the population. To do that, Yamanaka needs to find donors who have two identical copies of each of three key genes that code for immune-related cell-surface proteins called human leukocyte antigens (HLAs). He calculates that he will have to sift through samples from some 64,000 people to find 75 suitable donors.

Using blood from Japans eight cord-blood banks will make that easier. The banks hold some 29,000samples, all HLA-characterized, and Yamanaka is negotiating to gain access to those that prove unusable for other medical procedures. One issue remains unresolved: whether the banks need to seek further informed consent from donors, most of whom gave the blood under the understanding that it would be used for treating or studying leukaemia. Each bank will determine for itself whether further consent is needed.

Yamanaka has already built a cell-processing facility on the second floor of CiRA and is now applying for ethics approval from Kyoto University to create the stock. Takafumi Kimura, a CiRA biologist and head of the projects HLA analysis unit, says that the team hopes to derive the first line, carrying a set of HLA proteins that matches that of 8% of Japans population, by next March.

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Stem-cell pioneer banks on future therapies