Chimeric macaques give new meaning to phrase, 'I'll be a monkey's uncle'

They look like ordinary baby rhesus macaques, but Hex, Roku and Chimero are the world's first chimeric monkeys, each with cells from the genomes of as many as six rhesus monkeys.

Until now research on so-called chimeric animals, or those that have cells with different genomes, has been limited to mice; a recent procedure produced mice using cells from two dads.

The researchers turned to monkeys for more insight into the capabilities of embryonic stem cells. Most experiments on stem cell therapies are based on mice, and the researchers wanted to understand whether primate embryonic stem cells respond the same way as those of mice do.

To create the chimeric monkeys, researchers essentially glued together cells from individual rhesus monkey embryos and then implanting these mixed embryos into mama monkeys.

The key was mixing cells from very early-stage embryos, or blastocysts, that consisted of just two to four cells – each one of the cells still totipotent, capable of transforming into a whole animal as well as the placenta and other life-sustaining tissues. (This is in contrast to pluripotent stem cells, which can differentiate into any tissue type in the body, but not certain embryonic tissues or entire organisms.)

"The cells never fuse, but they stay together and work together to form tissues and organs," said Shoukhrat Mitalipov of the Oregon National Primate Research Center at Oregon Health & Science University. "The possibilities for science are enormous." [Images of the Chimeric Monkeys]

Try, try again

The researchers first tried creating chimeric monkeys using the process for chimeric mice. In this procedure, embryonic stem cells are injected into a host embryo after they have been cultured for as long as decades. These stem cells will mix with the host embryo's cells to produce tissues and organs and ultimately offspring. When these offspring are mated, the resulting offspring have cells derived solely from the implanted stem cells. If you were to pluck two cells from a chimeric mouse's body, you could get two different genomes  –  complete sets of chromosomes and genetic information.

But the methods that work to create chimeric mice failed in rhesus monkeys, leading to offspring with cells only from the host embryo.

"Unfortunately that didn't work," Mitalipov told LiveScience in a telephone interview. "We produced offspring that way and they didn't show any contribution of stem cells." The stem cells seemed to have gotten lost somewhere, he said.

The researchers guessed that the culturing somehow had changed these embryonic stem cells. So they recovered stem cells from an embryo's inner cell mass (rather than from the freezer after being cultured) and, without culturing them, injected the stem cells into a host embryo.

Rather than one chimeric monkey infant, the result was two separate fetuses — twins.

Finally, the researchers hit on a successful method, using early blastocysts that had split into no more than four separate cells. They took individual cells out of these clumps and aggregated them back together, mixing and matching between three and six individuals to create 29 new blastocysts. The researchers picked the 14 strongest-looking of them and implanted them in five surrogate mother monkeys. 

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