Chimeric mice are one of the most important tools in biological research. By studying composite animals with tissues from distinct genetic lineages, scientists have gained important insights into the molecular mechanisms of disease. This powerful biomedical research tool has largely been restricted to rodents and farm animals that are distantly related from humans, and, thus, might not best approximate human disease. Now, however, rhesus monkeys have joined the chimera club—an advance that researchers hope will help bridge the gap between mice and humans.

“It is not enough to jump from mouse right to human in transplanting tissues,” says Shoukhrat Mitalipov, a developmental biologist at the Oregon National Primate Research Center in Beaverton who led the study. “We need primate models to know if tissues are truly functional.”

In their study, Mitalipov and his colleagues plucked cells from early-stage monkey embryos containing only four cells each. They then mixed the cells together into aggregates containing cells from between three and six different embryos. After growing the cells up to the blastocyst stage, they implanted 14 of the cell clusters into five females. The scientists terminated three of the pregnancies for genetic analysis, but the other two monkeys gave birth to healthy baby boys: a pair of twins named Roku and Hex (pictured here), and a singleton name Chimero. These monkeys were indeed chimeric—with some cells originating from female embryos, too—as the researchers detected multiple genotypes in the animals’ blood cells. The findings were published today in Cell.

This method stands is in stark contrast to that typically used to create chimeric rodents. In mice and rats, scientists usually inject cultured embryonic stem cells into developing embryos from another animal strain. Although Mitalipov has cloned monkey embryos in the past, and even derived embryonic stem cells, his attempts to create chimeric monkey fetuses using cultured embryonic stem cells failed repeatedly because the stem cells didn’t incorporate properly into the host embryo.

Rhesus monkeys are currently used for a host of different biomedical applications, including studies of HIV and influenza viruses. For such studies, especially those on drug therapies, which often now go directly from mouse to human testing, the addition of a chimeric monkey model will be a crucial bridge for vetting the potential translation of findings to humans.

Image courtesy of Oregon Health & Science University

Cross-posted from the Nature News Blog

An American university scientist was arrested on 27 December, accused of supplying stem cells for use in unapproved therapies.

The US Department of Justice says Vincent Dammai, a researcher at the Medical University of South Carolina (MUSC) in Charleston, supplied the stem cells without the approval of his university or of the US Food and Drug Administration. Two other men, Francisco Morales of Brownsville, Texas, and Alberto Ramon, of Del Rio, Texas, were also arrested this week as part of the case. A fourth man, Lawrence Stowe of Dallas, Texas, has been charged and a warrant is out for his arrest, according to an FBI press release.

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Crossposted from Nature’s news blog

A company that pioneered embryonic stem cell research is walking out on the field it helped to create. Geron, based in Menlo Park, California, announced yesterday that it would kill off its stem cell program — and its landmark clinical trial of a treatment for spinal cord injuries — so that it can focus on cancer therapies.

For supporters of the technology, Geron’s exit is a blow. “This is very unfortunate for the field,” says Robert Lanza, chief scientific officer of Advanced Cell Technology, the only other embryonic stem cell company with regulatory approval to conduct clinical trials in the United States. “It is a big deal. It certainly puts a lot of pressure on us to deliver now.”

Geron was the first company to gain approval from US regulators to conduct a clinical trial using human embryonic stem cells. The company has treated four patients with spinal cord injuries since it launched the trial in 2010, and has reported that the treatments appear to be safe though they have not yielded any improvement in spinal cord function. The trial was only designed to test safety, however, and Geron has made it clear from the start that the company did not expect the treatment regimen — including the number of cells injected — to be sufficient to relieve paralysis in the ten patients it ultimately aimed to treat in its first trial.

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Researchers in New York have succeeded where the disgraced South Korean Hwang Woo-suk failed. They have successfully derived the world’s first stem cells from a cloned human embryo. But, notably, the new stem cells are not suitable for therapeutic use because they contain three sets of chromosomes, instead of the regular two.

In work published today in Nature, a team led by Dieter Egli at the New York Stem Cell Foundation took skin cells from healthy and diabetic volunteers and inserted the cells’ nuclei into unfertilized human eggs. Within a few days cloned embryos developed allowing researchers to pluck out and propagate stem cells. These cells displayed all the hallmarks of embryonic stem (ES) cells, including characteristic gene activity and the ability to differentiate into all three germ layers in the teratoma test — the gold standard of pluripotency.

“It is the first demonstration that human oocytes have the ability to reprogram a specialized adult cell to the state of a pluripotent stem cell,” Egli told Nature Medicine.

However, the cells are not your typical ES cells: in addition to the two sets of chromosomes derived from the skin cells, the stem cells contained a full set from the egg as well, making them triploid. These new cells have been dubbed “somatic cell genome, oocyte genome pluripotent stem cells”, or soPS (rhymes with ‘hops’) cells for short. As triploid cells, they are not true donor-matched, patient-specific cells, and have a higher chance of immune system rejection when transplanted. This is likely to prove a sticking point, according to Robert Lanza, chief scientific officer of Advanced Cell Technology, a Santa Monica, California-based stem cell biotechnology company, who points out that personalized cell-therapy “is the whole purpose of this technology.”

Method makeover

This failure to create ES cells with only the donor cell’s genome was not for lack of trying. In early experiments, Egli’s team attempted to create normal cloned embryos through a process known as ‘somatic cell nuclear transfer’ (SCNT), which involves removing the egg’s haploid nucleus before inserting the adult diploid nucleus. This technique has worked in many mammalian species, ranging from mice to nonhuman primates, and, indeed, it’s the method that scientists used to create Dolly the sheep. But when Egli’s group swapped the egg and skin cell nuclei in their unfertilized eggs, they found that all the resulting embryos stopped dividing after just 6 to 10 cells. Some research groups have used SCNT to create later-stage human embryos with better success. Yet, barring Hwang’s fraudulent claims in 2004, none have reported any success at creating stem cell lines from these clones.

In a clever workaround, Egli and his colleagues left the egg’s nucleus in place, and fused it with the nucleus taken from the skin cell. Around 20% of the triploid eggs developed to the blastocyst stage (a mass of 70–100 cells), demonstrating the viability of the manipulated embryos. From the 13 blastocysts the researchers created, they obtained two stem cell lines — one containing the DNA of a man with type 1 diabetes and another from a healthy adult male donor.

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Scotland first grabbed headlines in the stem cell world fifteen years ago with the cloning of Dolly the sheep. But Scotland’s stem cell successes didn’t end there. In 2003, scientific highlanders at the University of Edinburgh discovered Nanog, a critical pluripotency gene expressed in embryonic stem cells. And last year, doctors at Glasgow’s Southern General Hospital treated a patient in the first-ever regulated human trial for a stem cell stroke treatment.

Yet stem cell medicine in Scotland has also faced some quagmires in the moors. Five years ago, for example, embryonic stem cell pioneer Austin Smith moved to the University of Cambridge; then, the biotech company Stem Cell Sciences followed suit. But with the development of potential new stem cell therapies for multiple sclerosis and the prospect of a stem cell-based approach to make blood for transfusions, scientists in Scotland are starting to turn things around. And those efforts will be emboldened by the Scottish Centre for Regenerative Medicine, a new ₤59 million ($97 million) research and commercialization facility in Edinburgh slated to open this summer.

Earlier this year, organizers announced that Charles ffrench-Constant, a multiple sclerosis researcher at the University of Edinburgh, would replace Dolly cloner Sir Ian Wilmut as the center’s director. Ahead of the building’s launch, Nature Medicine spoke to ffrench-Constant to learn how he plans to advance stem cell medicine in the land of lochs and glens.

What milestones do you hope to meet at the new center over the next five to ten years?

I would like us to have dramatically improved our understanding of basic stem cell science, and use this knowledge to be able to take human embryonic stem cells or human induced pluripotent stem cells and convert them into very large numbers of specific cell types in the brain, liver or in the blood. We would also like to be able to do the same in skin and heart and then use those [cells] either for disease modeling purposes, drug discovery programs or put them directly into the patient. I would like to be able to tell you that these goals weren’t just feasible but also something that is practical.

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Korea’s disgraced cloning researcher, Woo-suk Hwang is apparently back in the lab, according to an exclusive from the Associated Press.

The article says Hwang and 30 of his former colleagues have set up shop outside Seoul and are hard at work deriving stem cell lines from pig and cow embryos. One of the scientists is quoted as saying what a pity it is that they can’t get their hands on human eggs—to which my response is “Chuh!”

In case you’ve forgotten, Hwang is the scientist who sucecssfully hoodwinked the whole world into believing first that his team had successfully derived embryonic stem cells from a cloned human embryo and then that they had created 11 patient-specific stem cell lines from people with different diseases. And they claimed to have done all this using eggs from willing volunteers, 242 eggs the first time and 185 the second.

It was all a big scam, of course. Much to everyone’s utter shock, there were no such cell lines. And and as it turned out later, Hwang had in fact used more than 2,000 eggs, and in many cases had either paid, duped or coerced women—including two graduate students in his lab—into donating them.

What I’m still shocked by is these 30 scientists who are still putting their faith in him. But maybe I shouldn’t be. Hwang was so good at seeming like the humble man of science, even playing the Asian card at times, that no one suspected a thing for years.

My colleague at Nature, David Cyranoski, first reported the ethical violations in May 2004, a year and a half before Hwang’s collaborator Gerald Schatten raised an alarm. During that time, most scientists believed that Nature had cooked up the allegations over jealousy that Hwang had chosen to publish in Science, a theory Hwang himself had floated. But as I reported in May 2005, some people in Korea saw him as a two-faced manipulator who “sells himself very well,” long before the West caught on.

It’s disturbing to see that Hwang still hasn’t given up on human eggs and cloning. Here’s hoping the government makes sure he he has to stick to pigs and cows.