February 2, 2017

Scientists say human-pig embryo could be first step toward growing human organs in animals

Daily Briefing

    Two new studies suggest that so-called chimeras, animals composed of two different genomes, could be a viable tool to help develop new medical therapies for humans, according to experts.

    Background

    Chimeras are a controversial topic in the scientific community. Some worry that human stem cells implanted into other animals could endow such animals with more intelligence or a human reproductive system. And "others think there's a symbolic or sacred line between human and animal genetic material that should not be crossed," the Washington Post's "Speaking of Science" reports.

    Since 2009, scientists have been prohibited from implanting human stem cells into monkeys. And in 2015, the National Institutes of Health (NIH) barred federal funding for human-animal chimera research. NIH released a draft rule last August that would loosen the research-funding ban, but it is unclear whether the Trump administration will support the change, NPR's "Shots" reports.

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    Some scientists strongly defend chimera research because of the potential medical benefits for humans: Those scientists believe growing human organs within animals could help alleviate the shortage of organs used for transplants. About 76,000 people in the United States are waiting for transplants, according to the New York Times. And HHS estimates that 22 people die each day waiting for an available organ.

    Study marks possible first step toward growing human organs in animals

    In one of the new studies, published last week in the journal Cell, scientists at the Salk Institute for Biological Studies successfully transplanted human stem cells into pig embryos, where they developed into human tissue—a possible first step toward growing human organs in animals that could be transplanted into humans, the Times reports.  

    For the study, researchers implanted a "dozen" stem cells at various stages of development into pig embryos. Researchers then implanted the embyros into sows, where they developed for three to four weeks.  According to the Times, the researchers used private funds for the study, enabling them to sidestep the NIH funding ban.

    The researchers found that "naïve" stem cells (those at the earliest stage of development) were "initially incorporated into the growing animal," "Speaking of Science" reports, "but [they] were indistinguishable in the developing pig four weeks later." And "primed" cells (those at the latest stage of development), did not propagate significantly.

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    But, they found stem cells at an "intermediate" stage of development took hold. Lead author Jun Wu estimates that one of every 100,000 intermediate cells implanted in the sows were human. However, the cells were not evenly distributed. They made up about 10 percent of the heart and 1 percent or less of the kidney and liver.

    Study demonstrates feasibility of interspecies organ transplants

    In the second study, a separate team of researchers from Stanford University and the University of Tokyo documented how they "reversed diabetes in mice by inserting pancreas glands composed of mouse cells that were grown in a rat," the Times reports. The study, published last week in Nature, is the first demonstration that interspecies organ transplants are possible, according to "Speaking of Science."

    For the study, the researchers implanted mouse stem cells into rat embryos that had been genetically modified not to produce a pancreas. This change allowed the mouse stem cells to fill a "niche," "Speaking of Science" reports, and develop into rat-sized pancreases made of mouse cells. The rats were healthy and developed normally.

    Next, researchers removed the part of the pancreas from the rats that produces a hormone similar to insulin and implanted it in mice which had been induced into diabetes. Because the pancreases were made of mouse cells, the mice only needed a few days of immunosuppressive drugs. "After that, [the mice] were able to live normally with healthy blood glucose levels for over a year—half a lifetime in human terms," "Speaking of Science" reports.

    According to the Times, the research team's next step is to repeat the experiment in pigs, which can develop organs better-sized for human use.

    Discussion

    Hiromitsu Nakauchi, the lead author of the pancreas study, said his finding were important because they build the case that chimeras have a useful purpose.

    "This is a form of transplantation we could do in the clinic with human patients someday," he said, although both he and Izpisua Belmonte, the lead author of the Cell study focused on pig embryos, cautioned that such progress is a long way off. Chimeras could likely be used more immediately to examine human embryogenesis, test drugs, and tracking the progress of a disease, they said.

    Nakauchi added that he hoped the new research would help overturn the current NIH ban and other restrictions that impede chimera research. "Finally we're able to provide a proof of principle that ... this approach of making organs … is possible and also safe and efficient," he explained, adding "we're not creating monsters."

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    Belmonte said implanting human stem cells into other animals to develop human organs seemed to have a more promising future than trying to grow such organs in the lab.  "In the last 18 years, hundreds of labs, including ours, have tried to generate different cell types from human pluripotent stem cells in the culture dish with a cocktail of factors" without success, he said. "So I thought, 'Why not let nature do the job?'"

    Rudolf Jaenisch, a stem cell expert at the Whitehead Institute, praised both of the studies. "I think this is very promising work in principle," he said (Wade, New York Times, 1/26; Kaplan, "Speaking of Science," Washington Post, 1/26; Stein, NPR, 1/26).

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