Researchers at Oregon Health Sciences University (OHSU) have created the world’s first chimeric monkeys, which may contain as many as six distinct genomes. Named Roku, Hex, and Chimero, these rhesus monkeys were produced by successfully aggregating multiple embryos and implanting the mixed embryo into a surrogate mother. Findings during the study also suggest that cultured embryonic stem cells (ESCs), which were previously thought to be capable of differentiating into any cell type, may not be potent as their pluripotent in vivo counterparts. The report is published online ahead of print in the January 20 issue of Cell.

Although Roku, Hex, and Chimero represent the world’s first chimeric monkeys, chimeric mammals including mice, rats, rabbits, sheep, and cattle have in fact been successfully produced as early as the 1970s. However, in contrast to mice, the most utilized and well-studied chimera model, principle investigator Shoukhrat Mitalipov of OHSU and the Oregon National Primate Research Center demonstrated that injection of rhesus monkey cultured ESCs or pluripotent cells derived from the inner cell mass (ICM) of a blastocyst into a host embryo failed to produce chimeric offspring. Instead, successful creation of monkeys such as Roku, Hex, and Chimero appear to require totipotency—the programming of a single cell that has the ability to divide and produce all the differentiated cells in an organism—that is transiently available in the four- or low-cell stage embryo. Mitalipov and colleagues therefore reason that embryo development and lineage commitment, whether from totipotency or pluripotency, is species-specific.

Mitalipov says it appears that primate embryos prevent cultured embryonic stem cells from becoming integrated as they do in mice. Their study also suggests that cultured primate and human embryonic stem cells, some of which have been maintained in lab dishes for as long as two decades, may not be as potent as those found inside a living embryo.

"We need to go back to basics," Mitalipov said. "We need to study not just cultured embryonic stem cells but also stem cells in embryos. It's too soon to close the chapter on these cells." For instance, he added, cultured embryonic stem cells are now considered the "gold standard" for comparisons to induced pluripotent stem (iPS) cells made by treating adult cells with relatively simple cocktails.

"We cannot model everything in the mouse," Mitalipov continued. "If we want to move stem cell therapies from the lab to clinics and from the mouse to humans, we need to understand what these primate cells can and can't do. We need to study them in humans, including human embryos." He emphasized, however, that there is no practical use or intention for anyone to produce human chimeras.

Watch Roku and Hex at play! (video is low-volume).

Roku and Hex from OHSU News on Vimeo.

Watch OHSU's Dr. Shoukhrat Mitalipov explain his research:

Soundbites: Shoukhrat Mitalipov from OHSU News on Vimeo.

Source.
Image of Roku and Hex in graphic from OHSU.