From Nature magazine

Fatu, a female northern white rhinoceros who lives in a Kenyan conservation park, is one of just seven of her kind left in the world. But millions of her stem cells, stored in a freezer in California, might one day help boost her population's ranks.



The northern white rhino (Ceratotherium simum cottoni) and another animal facing extinction, the drill monkey (Mandrillus leucophaeus), have become the first endangered animals to have their cells transformed into stem cells like those found in early embryos. These cells can be stored and multiplied in culture, and are theoretically capable of making any tissue in the body — including sperm cells that could be used in assisted captive breeding programmes. The work is published online today in Nature Methods.



About five years ago, Jeanne Loring, a stem-cell biologist at the Scripps Research Institute in La Jolla, California, was contacted by Oliver Ryder, a scientist at the nearby San Diego Zoo, who was keen to collect stem cells from endangered animals. Obtaining stem cells by sacrificing the fertilized embryo of an endangered species was out of the question, so Loring tried to think of other sources, but came up empty. "The prospect of getting bone marrow stem cells from a rhinoceros was kind of daunting," she says.



A couple of years later, in 2007, teams at the University of Kyoto in Japan and the University of Wisconsin in Madison, revealed that the cells called fibroblasts from human connective tissue could be coaxed into a state resembling that of an embryonic stem cell by activating a suite of reprogramming genes in the adult cells. Ryder's team had been preserving fibroblasts from endangered animals since the 1970s as part of a project called the Frozen Zoo, so the cell-reprogramming technology seemed like a good way to create stem cells from endangered animals, Loring says.



As a proof-of-principle experiment, Ryder gave Loring cells from Fatu and from a captive male drill monkey named Loon (who has since died). Drills are now found in the wild only in tiny pockets of western Africa, their numbers dwindling because of habitat loss and a thriving bushmeat trade.



Loring and her colleague Inbar Friedrich Ben-Nun at first assumed that human versions of the reprogramming genes would not convert rhino or drill fibroblasts to stem cells, so the team tried reprogramming the drill cells with genes from another monkey species, the rhesus macaque, and Fatu's fibroblasts with horse genes. Both attempts failed.



Reprogramming success

To Loring's surprise, however, the corresponding human genes did transform both animals' cells into embryonic-like stem cells called induced pluripotent stem cells (iPS cells). As proof of pluripotency, the researchers coaxed the drill and rhino iPS cells into making the three different kinds of simple tissues that produce all the other tissues in the body.



Loring does not plan to use the iPS cells of Fatu and of Loon to clone these individuals. Instead, the cells could be converted into germ cells for use in assisted breeding programmes to help diversify the gene pools of endangered species, she says. Healthy mice have been born this way, and Loring believes that, in time, the techniques will be made to work with other animals. "If everything falls into place and everything works, there is a way to generate new animals," she says.



"I think this is a very exciting development," says Robert Lanza, chief scientific officer of Advanced Cell Technology, based in Santa Monica, California, and part of a team that carried out the first cloning of an endangered animal, a guar bull named Noah, in 2000. When human iPS cells were first described, Lanza touted their potential for endangered species conservation in a letter to the journal Science, and he has even patented a technique to clone endangered animals from iPS cells, which he says he would license freely for conservation efforts.



No quick fix

William Holt, a reproductive biologist at the Zoological Society of London, is involved in a collaboration called the Frozen Ark, based at the University of Nottingham, UK, which culls DNA and cells from endangered animals. He doubts that iPS cells will save many threatened species, particularly those already on the brink of extinction like the northern white rhinoceros.



"To be honest I think it's a bit of a stunt," he says. Scientists know little about the reproductive biology of these animals, which is needed to support assisted reproduction programmes, and, with so few individuals remaining, there is little opportunity to learn more, he says.



Loring concedes that there are technological gaps to fill in before iPS cells can help save species. "I don't know how you could super-ovulate a rhino," she says. But she dismisses the notion that iPS cells from endangered animals are a gimmick. Even if the technologies to use them in assisted breeding aren't mature, the cells offer a way to preserve the genetic diversity of individual animals long after they have died.



Fatu, at least, isn't waiting for such breakthroughs: in January this year, she began mating with a male named Suni.

This article is reproduced with permission from Nature magazine. It was first published on September 4, 2011.