The finding could fundamentally change how we look at human stem cell tech: If chimeric monkeys require totipotent cells before they can come into being, it stands to reason that human embryonic stem cell therapy might also require totipotent stem cells to render cures. Indeed, the find suggests that testing human therapies on mice and other mammalian species may have sent us down the garden path.
The Chimeric Advantage
The ability to create chimera from stem cells not only in mice but in other animals, including primates, could prove to be a major advance in biomedical science. In a 2009 study, University of Georgia at Athens cloning expert Steve Stice created 29 chimeric piglets by injecting pluripotent stem cells into pig embryos before implanting them into a surrogate womb.
Although it wasn’t the first time chimeric pigs were created, it was the first time they came about using cloned pluripotent cells. And because pigs are genetically closer to humans than mice are, success in creating chimeric pigs from stem cells offered renewed hope that the technology could lead to better pharmaceutical testing or stem cell therapies.
“If we’re going to bring stem cells to the human clinic, we need to know exactly how those stem cells will work."
But the most significant part of these finds, says bioethicist Jason Robert of Arizona State University, is that research on rodents (or pigs) may not be directly applicable to humans. Even rhesus macaques, he says, “are not the ideal nonhuman primate to study, since they are not as closely related to us as chimpanzees. We need to ask if we’d learn more if we studied other animals—more expensive animals that are closer to humans. If our ultimate goal is to take human cells and transplant them into human subjects, we want to know ahead of time that they will behave and integrate well.”
Mitalipov couldn’t agree more. “Stem cell therapies hold great promise,” he says, from possible treatments for brain disease to heart disease and age-related disorders. “No drug could restore functional tissue the way that stem cells could.” But given the difficulty of achieving monkey chimeras from pluripotent cells, Mitalipov thinks we might need to derive an entirely new stem cell class for regenerative medicine in humans: the all-powerful totipotent cells.
Meanwhile, the monkeys will be weaned and raised to adulthood. “We will see if these three monkeys can have normal offspring. We will want to see if these chimeras persist through the generations,” Mitalipov says.