The Japanese government is backing an ambitious but also a controversial stem cell research that would allow scientists to grow human organs in animal subjects, a field of study that was, up until recently, banned.
The ambitious goal is led by stem cell scientist, Hiromitsu Nakauchi together with teams at the University of Tokyo and Stanford University in California.
The basic idea is that Nakauchi and his team will be creating animal embryos that contain human cells and transplant them into a surrogate.
The whole process can be likened to what we know as an in vitro fertilization or an IVF, where the process of fertilizing a female egg cell is performed outside the body, in vitro. Then, doctors inject the fertilized egg cell back to the woman’s uterus, where it can develop until term.
However, for human-animal embryo experiments, instead of fertilizing an egg cell, scientists have a genetically-altered animal embryo that’s meant to not to develop a certain organ.
In Nakauchi’s experiment, these animal embryos are meant not to develop a pancreas. Instead, they will be infusing that embryo with human induced pluripotent stem (iPS) cells into the animal fetus.
The iPS cells are reprogrammed to develop into a human pancreas organ, as the fetus develops inside the IVF-host animal until they are delivered to term and will continue to do so after.
Nakauchi is planning to initially test this theory of growing human organs in rat and mouse embryos and then transplant those embryos into surrogate mothers.
The goal is for the rodent embryo to use the human cells to build itself a pancreas, and for two years, the team plans on watching these rodents develop and grow — carefully monitoring their organs and brains in the process.
If successful, Nakauchi’s experiment can pave the way to offer transplant-quality organs at a more accessible rate.
Organ transplants are often the last resort for patients who are suffering from organ failure and other medical illnesses, but the only ethically acceptable way of receiving the life-saving procedure is when someone dies, or family members to willing donate them (kidney, liver, etc.).
Other than that, patients need to get listed by priority, which often becomes a long and tedious process.
Even after going through an organ transplant, results could be uncertain as some bodies reject the organ and render them useless.
On the other hand, Nakauchi’s experiment is still nowhere near a done deal. Although it can offer an ideal solution, the field of study is barely developed, and multiple technical hurdles need to be overcome.
Mainly, human-animal organs is not an entirely new idea. It has been tried in the US in the past, where rules are more relaxed — though the National Institutes of Health has had a moratorium on funding this type of work since 2015.
In 2018, the American Association for the Advancement of Science reported that they had conducted and performed the same experiment into sheep embryos. However, the hybrid embryos — grown for 28 days — contained very few human cells, and nothing resembling organs.
According to Nakauchi, this is probably because of the genetic distance between humans and sheep.
Jun Wu, who researches human-animal chimeras at the University of Texas Southwestern Medical Center in Dallas said, “it doesn’t make sense to bring human-animal hybrid embryos to term using evolutionarily distant species such as pigs and sheep because the human cells will be eliminated from host embryos early on.”
“Understanding the molecular basis and developing strategies to overcome this barrier will be necessary to move the field forward,” the researcher added.
Nakauchi says that he will address the problems noted in the 2018 experiments and will be testing his at subtly different stages with genetically-modified iPS cells.
”This will be a long and tentative process, ” Nakauchi said. ”We don’t expect to create human organs immediately, but this allows us to advance our research-based upon the know-how we have gained up to this point,” Nakauchi told a Japanese outlet.
With more than 116,000 patients on the transplant waiting list in the United States alone, Nakauchi hopes his idea can transform lives.
But with every new developing advancement in the medical field, Nakauchi’s plan attracts ethical concerns, especially that relating to the overall health of the animal carrying the iPS cells. People are concerned about the human cells spreading to other parts of the animal, such as the brain and would result in humanized animals.
Nakauchi, however, doesn’t think this is going to happen. Last year, he and his colleagues at Stanford successfully made the first human-sheep embryo, and although it was destroyed after 28 days, the hybrid contained no organs and very few human cells — only about one in 10,000 or less.
Nevertheless, Nakauchi said he and his team are trying to target this treatment to the pancreas only, and plans to proceed slowly and subtly cross different stages of development. If they detect more than 30 percent of the rodent brains are human, they will suspend the experiment.
“We are trying to ensure that the human cells contribute only to the generation of certain organs,” Nakauchi explained.
“With our new, targeted organ generation, we don’t need to worry about human cells integrating where we don’t want them, so there should be many fewer ethical concerns.”