A drug derived from bone marrow cells has failed two late stage clinical trials, representing a major setback for stem cell medicine. The drug, developed by Osiris, a stem cell company based in Maryland, is considered the closest to market of all the stem cell-based products in human testing.

The announcement follows another significant setback for the field. Last month, Geron, an embryonic stem cell company based in California, announced that its clinical trial for spinal cord injury--set to become the first human trial of human embryonic stem cells--was put on hold by the Food and Drug Administration after animal studies showed that the treatment was linked to increased development of small cysts at the injury site.

Osiris's drug, called prochymal, is a preparation of mesenchymal stem cells (MSCs) isolated from the bone marrow of healthy young adult donors. Research in animals suggests that these cells can reduce inflammation and spur tissue healing by stimulating the release of molecular growth factors.

The drug is also being tested in clinical trials for myocardial infarction, chronic obstructive pulmonary disease (COPD) and type 1 diabetes. Osiris halted a late-stage clinical trial of prochymal for Crohn's disease, a form of inflammatory bowel disease, earlier this year because of the high placebo response rate.

According to an article in The New York Times:

Stem cells, particularly in the form of bone marrow transplants, are already used in medicine. Osiris is hoping that Prochymal will become the first stem cell product approved by the Food and Drug Administration and sold as a mass-produced pharmaceutical product.

But the failure in the two trials could make it hard to reach that goal. Both trials tested Prochymal as a treatment for graft-versus-host disease, which occurs when immune cells in donated marrow attack the recipient's organs as foreign tissue.

In one trial, in which Prochymal was used along with steroids, 45 percent of patients responded to Prochymal and steroids compared with 46 percent who had a response to steroid and a placebo.

In a second trial, in which Prochymal was tested in patients who were not benefiting from steroids, 35 percent of those getting the drug had a resolution of graft-versus-host disease for at least 28 days, compared with 30 percent getting the placebo. The difference was not statistically significant.

Osiris said, however, that in the second trial, the drug did provide a statistically meaningful benefit in patients having graft-versus-host disease that specifically affected their livers or their gastrointestinal tracts.

A mouse derived from iPS cells. Credit: Nature

Two groups of researchers from China have independently shown that induced pluripotent stem (iPS) cells--a newly-developed type of stem cell derived from adult cells--can grow into a fully formed mouse. The findings show that these cells are just as flexible in their fate as embryonic stem cells. The findings were published today in the journals Nature and Cell Stem Cell.

iPS cell reprogramming--a technique first developed in Japan in 2006--has generated a great deal of excitement. Unlike embryonic stem cells, iPS cells can be generated without the destruction of a human embryo and thus circumvent the ethical issues that have mired much of stem cell research. While iPS cells have been shown to be capable of developing into many different cell types, they had not been shown to be equal to embryonic stem cells--until today.

The research shows that the new type of stem cells "satisfy the most stringent criteria of embryonic stem cells--the ability to make a mouse entirely from cells in a petri dish," said George Daley of the Harvard Stem Cell Institute and Children's Hospital of Boston to the Associated Press.

According to a news article at Nature.com:

[Researchers] created a 'tetraploid' embryo by fusing two cells of an early-stage fertilized embryo. A tetraploid embryo develops a placenta and other cells necessary for development, but not the embryonic cells that would become the body. It is, in essence, a car without a driver.

When implanted into these embryos, the iPS cells began to steer development. The developing embryo was transferred to a surrogate mother, and 20 days later a mouse was born. It was black, like the mice used to create the iPS cells and unlike the white mice used to create the tetraploid embryo. DNA tests confirmed the mouse, named Xiao Xiao or 'Tiny', had arisen from the iPS cells.

While successful, the process was difficult. In one of the papers, researchers report 22 live births from 624 injected embryos, a success rate of 3.5%.

According to Nature:

The mice seem to have a high death rate, with some dying after just two days, and others displaying physical abnormalities, details of which the team would not reveal. But some of their mice passed one of the most fundamental tests of health: all 12 mice that were mated produced offspring, and the offspring showed no abnormalities. The team says it now has hundreds of second-generation, and more than 100 third-generation, mice. The team found no tumours in the mice, although they have not systematically looked for them.

...

Both groups are now trying to understand what differences between iPS cells and embryonic stem cells might explain the abnormalities, high death rates, low efficiency rates and the fact that most iPS cell lines don't seem to work in making mice. Zeng and Zhou found, for one thing, that timing was important: cells that formed iPS cell colonies quickly -- after 14 days -- were successful, whereas those that formed colonies after 20 or 36 days did not work. Gao suggests that "aberrant reprogramming" might be to blame, at least for the low efficiency rates.

For more on IPS cells, see Medicine's New Toolbox.

In what is thought to be a first for the country, New York State has announced that women who donate eggs for research can be paid up to $10,000. Obtaining human eggs for research has been a huge hurdle for scientists attempting therapeutic cloning through somatic cell nuclear transfer (SCNT), the process used to create Dolly the cloned sheep. Non-binding guidelines put forth by the National Academy of Science prohibit paying women for eggs used in stem cell research. The issue--and the science--is so highly charged that most scientists working in the field have kept quiet about the details of their research, and it's unclear how many women have come forward to donate eggs thus far.

Scientists want to use SCNT to generate cloned human stem cells. In the process, the DNA from an adult cell, such as a skin cell, is inserted into a human egg that has had its DNA removed. The fertilized egg then begins to develop similarly to a regular embryo, and scientists can harvest stem cells several days later. The resulting cells are genetically matched to the adult tissue donor, and could therefore be used for cell transplants without the risk of immune rejection.

The creation of induced pluripotent stem cells (iPS cells)--a technique developed over the last few years to make stem cells from adult tissue without the use of eggs or embryos--has to some degree pushed the issue of egg donation to one side. These cells resemble embryonic stem cells in their potential to become many different types of tissue and are also genetically matched to the cell donor. But scientists say cloning is still important; they want to compare iPS cells and cloned cells, for example. In animal research, cloned stem cells have been studied much more extensively than iPS cells, which are still relative newcomers and appear to be highly variable in their ability to differentiate and self-renew.

Paying women for egg donation has been a highly controversial issue, with some opponents saying that payment will create a financial incentive for women to donate eggs. But supporters point out that women are already paid for egg donations for in vitro fertilization. Scientists working in the field say that recruiting women for egg donation--a potentially painful process with some risk--has been unsuccessful.

According to an article in the New York Times,

"There are many questions you can only answer by studying human eggs," said Dr. George Q. Daley, a stem cell researcher at Harvard and at Children's Hospital Boston. "I think it's a gold step for New York State, and it will mean a tremendous advantage for New York." Dr. Daley's research has so far used poor-quality eggs discarded after in vitro fertilization, a process he said has yielded modest returns but no stem cells.