In 1972, a group of forward-thinking conservationists in San Diego began freezing skin samples from endangered species. The hope was that science would eventually find a way to use the cells to help revive these fragile populations.
Jeanne Loring and collaborators at Scripps Research Institute have taken a key step toward fulfilling that hope by creating stem cells from frozen skin cells of two such species—the silver-maned drill monkey and the northern white rhinoceros.
In the near term, the researchers plan to build a frozen zoo of stem cells that scientists can use to study the animals’ genomes, and perhaps to create stem-cell therapies for the animals. (Drill monkeys living in captivity often suffer from diabetes, a highly active area of research in the human stem-cell field.)
In the longer term, the researchers hope to be able to use the cells to create sperm and eggs, which would be incorporated into breeding programs to boost the genetic diversity of severely limited populations; the white rhinoceros is on the verge of extinction, with only seven animals alive today. They haven’t bred in years.
“To think of the foresight they had in the 1970s to start this program,” says Loring, director of the Center for Regenerative Medicine at Scripps. At that point, “no genome had been published, and the concept of this ever happening was science fiction.” Her team aims to generate stem cells for at least 10 other species, including snow leopards and some species of elephants. San Diego’s “Frozen Zoo” houses tissue samples from more than 800 species.
To create the stem cells, Inbar Friedrich Ben, a postdoctoral researcher in Loring’s lab, used a technique first developed in 2007 called induced pluripotent stem (iPS) cell reprogramming. A handful of genes that are normally active in the developing embryo are expressed in a differentiated cell, such as a skin cell, causing that cell to revert back to its undifferentiated state.
Much to their surprise, the human genes that are typically used to reprogram human cells could also reprogram skin cells from both the monkey and the rhinoceros, though at a much lower efficiency. Still, the reprogrammed cells showed the defining characteristics of induced pluripotent stem cells; they could both differentiate into various cell types and generate more of themselves. The research was published this week in Nature Methods.
“This method paves the way to save endangered species such as the giant pandas, cheetahs, tigers, gorillas in East Africa, and even extinct species like the bucardo mountain goat,” says Robert Lanza, chief scientific officer at Advanced Cell Technology. “It will open the way for new strategies to help maintain biodiversity and to respond to the challenges of large-scale extinctions ahead.” Lanza was not involved in the study.
For animals like the white rhinoceros, each death represents a serious loss to the gene pool, which in turn weakens the population. By creating stem cells from animals that died, “their genes could be reintroduced to maintain the survival and genetic diversity of the species,” says Lanza. “The bucardo mountain goat could be resurrected using this technology if combined with an ordinary goat breeding program.”
Creating a new animal from a stem cell is likely a long way off. Researchers would need to first create sperm or eggs from the stem cells and then use them with sperm or eggs from a living animal to create an embryo. Fertility scientists are avidly searching for ways to develop sperm and eggs from stem cells in order to treat human infertility, and Loring hopes those technologies could be applied to these animals.
Prior to the development of iPS cell reprogramming, Lanza’s group used cloning—the method used to create Dolly the sheep—to try to reproduce two species of wild cattle; the guar and the critically endangered banteng. But cloning is ill-suited to species conservation, since it is a technically challenging process that often results in sick or deformed animals.
Lanza says another way to use stem cells to propogate endangered species would be to inject the cells of a more common, related species into the embryo, and then use various experimental techniques to coax the cells descended from the endangered animal to grow into a fetus. His team has shown this approach works in mice.