Researchers report they have generated the first confirmed embryonic stem cells from an adult primate, suggesting that it may be only a matter of time (and eggs) before they perfect the same technique on humans.
Using a process called somatic cell nuclear transfer (SCNT), a team from Oregon Health & Science University (O.H.S.U.) in Portland implanted the contents of individual skin cells from adult male rhesus macaques into each of 304 macaque egg cells stripped of their genetic material. In two cases, according to the study, the hijacked eggs grew into early-stage embryos that yielded embryonic stem cell lines, indicating that the hosts successfully reprogrammed the skin cell DNA into an embryonic state.
The journal Nature published the findings online today, along with a separate genetic analysis corroborating the cloned nature of the cells.
"This unequivocally shows you can generate stem cells from primates, and we're primates," says stem cell biologist Robert Lanza, chief scientific officer of the Worcester, Mass., company Advanced Cell Technology, who was not involved in the research.
"It's a giant step toward showing that human therapeutic cloning is possible," he added, referring to the concept of creating stem cells matched to an individual's immune system to repair tissue damaged in spinal cord injuries and by diseases such as diabetes, Parkinson's and Alzheimer's.
Senior study author Shoukhrat Mitalipov calls the result a proof of concept. "I'm quite sure it will work in humans," he says, but notes that the process is still very inefficient. "Basically it comes [down] to how many eggs you would need to derive one embryonic stem cell line." (In this case, 152.)
Mitalipov says his goal is to engineer better primate models of human disease by cloning adult rhesus monkey cells that have been genetically altered to mimic neurological and other disorders that are otherwise difficult to study in living humans or other animals. He says that his team has yet to try to impregnate female monkeys with embryos derived using the new method.
A group from O.H.S.U. reported in 2000 that it had achieved a kind of primate cloning by splitting an eight-cell monkey embryo into four two-cell embryos, only one of which came to term. But researchers have struggled to clone nonhuman primates by SCNT, used in the 1997 cloning of Dolly the sheep.
After two earlier published attempts that led to early-stage embryos but not confirmed embryonic stem cells, Mitalipov and colleagues took steps to preserve a protein complex believed to help primate eggs restructure transplanted DNA, and employed a new imaging system to observe the egg's chromosomes directly instead of by staining them or using ultraviolet light, which might damage DNA.
The two newly reported cell lines developed into several types of tissue in culture dishes, including heart and brain, and when injected into mice generated teratomas (tumors made of the three embryonic tissue types). The cells had the genetic markers of clones, not of fertilized embryos or parthenotes, the latter of which derive only from the egg, according to the genetic analysis by researchers at Monash University in Australia.
Three teams of scientists reported earlier this year that they had directly reprogrammed adult mouse skin cells into embryonic cells, although the process involved viruses and cancer-causing genes.
In a commentary accompanying the new study, Dolly cloner Ian Wilmut and his co-worker Jane Taylor of the University of Edinburgh in Scotland wrote that "a modified approach to direct reprogramming…is likely to be the ultimate method of choice for producing human stem cells."
Lanza agrees but says that in the meantime SCNT remains a viable approach—although limited by the number of women willing to donate eggs to research.
Some scientists had proposed that SCNT might have hit a wall with primates, but Lanza says the new result shows that "primates are no different than other species. You just need to work out the unique biology and physiology." Meaning that humans could be next.