January 6, 2012
Researchers Create World’s First Chimeric Monkeys
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A team of scientists from Oregon Health & Science University (OHSU) have created the world´s first chimera monkeys in the lab using embryos of several individuals and implanting them into female monkeys.
The research, to be published online in the journal Cell this week, provides significant information about how early embryonic stem cells develop and take part in formation of the primate species. The team from OHSU´s Oregon National Primate Research Center successfully delivered three chimeric monkeys -- a singleton and twins -- that were reportedly healthy, and with no apparent birth defects following the controversial research.
The singleton was named Chimero, and the twins Roku and Hex. The chimeras have tissues and organs made up of cells that come from up to six distinct primate genomes. Lead researcher Shoukhrat Mitalipov said the cells never fuse, but work together to form tissues and organs. “The possibilities for science are enormous,” he told Ian Sample, science correspondent for The Guardian newspaper.
While all three monkeys are biologically male, blood tests reveal that Roku carries both male and female cells.
While chimeric animals were first created by researchers in the 1960s, the team of scientists believe their research is the first to successfully create chimeric monkeys. Since scientists were first able to produce chimeric mice in the 60s, others have gone on to produce chimeric versions of rats, rabbits, sheep and cattle.
Mitalipov and his colleagues produced the chimeras by carefully pushing four-day-old embryos together in a culture dish and waiting for them to grow. Within a couple of days, 90 percent of them had grown into early stage embryos called blastocysts that contained at least twice as many cells as usual.
The team then implanted the embryos into five female rhesus monkeys, all of which became pregnant. Tests confirmed that all of the animals´ organs and tissues contained cells from more than one embryo.
“This is an important development - not because anyone would develop human chimeras - but because it points out a key distinction between species and between different kind of stem cells that will impact our understanding of stem cells and their future potential in regenerative medicine,” explained Mitalipov, an associate scientist in the Division of Reproductive and Developmental Sciences at ONPRC.
Chimeras are important for studying embryonic development, but research has largely been restricted to mice.
Mitalipov´s initial efforts to produce chimeric monkeys by introducing cultured embryonic stem cells into monkey embryos failed. The embryonic stem cells the team tried and failed with were at a developmental stage known as “pluripotency.” This means they can transform into any tissue type in the body, but cannot turn into the placenta or an entire animal.
They were only able to make monkey chimeras when they mixed cells from very early stage embryos, in which each individual embryonic cell was “totipotent.” The totipotent cells are capable of giving rise to a whole animal as well as the placenta and other life-sustaining tissues. It appeared that primate embryos prevented cultured embryonic stem cells from becoming integrated as they do in mice.
The study also suggests that cultured primate and human embryonic stem cells, some of which have been maintained in labs for as long as two decades, may not be as potent as those found inside a living embryo.
The difficulties Mitalipov´s team faced could herald future problems in using embryonic stem cells to grow new tissues in humans. While stem cells inside embryos can grow into any tissue or organ, lines of embryonic stem cells cultured in labs seem to lose this ability, at least to some extent.
“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,” said Mitalipov.
Professor Robin Lovell-Badge, from the UK National Institute for Medical Research in Mill Hill, called Mitalipov´s research “very important.”
“Assumptions about the way human embryos develop have always been based on the mouse,” Lovell-Badge, who was not involved in the new study, told BBC News. He added, however, that this could be a “dangerous assumption.”
Mitalipov´s research holds promise for future therapies, such as replacing damaged nerve cells in those who have been paralyzed due to spinal cord injury and perhaps those with brain cells lost in Parkinson´s Disease.
“As we move stem cell therapies from the lab to clinics and from the mouse to humans, we need to understand what these cells do and what they can´t do and also how cell function can differ in species,” said Mitalipov.
Image Caption: Roku & Hex. Credit: Oregon Health & Science University
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