TOKYO— A scientist pioneering research toward generating human organs in pigs has cleared one hurdle in gaining approval to continue his research in Japan. But he is still concerned that finalizing new research guidelines will take too long, so he is considering conducting the key experiments in the United States.
Stem cell biologist Hiromitsu Nakauchi of the University of Tokyo has been pursuing the idea of implanting human pluripotent stem cells, which can differentiate into any of the cells in the human body, into pig embryos engineered to be incapable of developing their own pancreases. If the technique works, the stem cells will develop into human pancreases in the pig fetus. After a piglet's birth, the pancreas would be harvested and islet cells isolated for transplantation into human type 1 diabetes patients.
In a 2010 Cell paper, Nakauchi's team described growing rat pancreases, using rat stem cells, in apancreatic mouse embryos. And in a paper in the Proceedings of the National Academy of Sciences (PNAS) this past February, the team reported generating pancreases for one species of pig in apancreatic embryos of a different pig species. Nakauchi is focusing on pigs because their organs are similar in size to those of humans.
The next step would be using either human embryonic stem cells or human induced pluripotent stem (iPS) cells, which are derived from a patient's own skin cells, in the engineered pig embryos. Using patient-specific iPS cells would theoretically avoid the problem of tissue rejection because the generated pancreas would genetically match the recipient. Nakauchi says that to the best of his knowledge, he is the first to try this approach to generating human organs. If it works, it could be applied to the heart and other body parts.
Current Japanese national guidelines governing stem cell research allow mixing human and animal material in vitro but forbid in vivo experiments. "I have been asking the government to change the guidelines for 2-and-a-half years," Nakauchi says. At a meeting on 18 June, the Expert Panel on Bioethics of the Council for Science and Technology Policy, the nation's highest science advisory body, took a step in that direction by recommending that the guidelines be changed. Producing new regulations, however, involves several steps and would likely "take another year or two," Nakauchi says.
And a favorable decision is not guaranteed. Despite generous government support for regenerative medicine, including work on iPS cells, Japan's conservative bureaucracy "doesn't want to take risks," Nakauchi says. For example, at the end of May, a Ministry of Health panel, citing safety concerns, put off a decision to approve what would be the world's first clinical study using iPS cells. Researchers at the RIKEN Center for Developmental Biology in Kobe plan to generate replacement retinal pigment epithelial cells from iPS cells taken from patients suffering age-related macular degeneration. The health ministry panel may revisit that decision next month.
Nakauchi knows that for his research, time is of the essence. His PNAS paper demonstrated the basic principle, and he knows that competitors in other countries are now picking up the ball. With approval to pursue this research at least temporarily blocked in Japan, Nakauchi says that he is investigating the possibility of doing the human-pig embryo experiments in the United States, which permits such experiments so long as they are approved through routine institutional reviews. He declines to say where, because plans are not finalized. However, one of the co-authors on the PNAS paper, Leonard Herzenberg, is on the faculty at Stanford University, in California, where Nakauchi did a postdoc.
Nakauchi recognizes that he is stepping into controversial territory. "People think we're making a human-pig monster," he says, although most accept the idea once he explains what they are trying to do. The critical unanswered question is whether this technique will produce functional human pancreases. If it does, extensive safety testing would suggest that use in the clinic is 5 to 10 years away, he says.