General Research Updates 9/12/05-9/16/05

Tracking Stem Cell Movements:

The Johns Hopkins Gazette reported on research done at Johns Hopkins tracing stem cells’ movement throughout the body. Researchers gave dogs in whom heart attacks had been induced stem cells with both a radioactive tracer and an MRI contrast agent. They then used SPECT, or single photon emission computed tomography, combined with CT (computed tomography) to see where the stem cells migrated to in the dogs. The stem cells were distributed from the lungs to the heart within 24 hours, but also appeared in other organs, including the liver, kidney, and spleen. The article also appeared in the RxPG News. The original study was published in the September 6 issue of Circulation.

Mice Cells and Sheep Hearts:

A study in this week’s issue of the Lancet says that French researchers have used embryonic stem cells from mice to repair damage in sheep’s hearts. This has been picked up by several media sources.

Hype and Hope gives a short summary, reporting that nine sheep were injected with mouse stem cells and had healthier heart tissue a month later than the control group. An article on Nature.com gives more detailed background of the issue: heart attacks damages muscles and blood vessels. Stem cells from patients’ own blood marrow have been used in humans to try to treat the damage, but it has not been consistently successful. Studies with embryonic stem cells have showed that they worked in rodents to improve blood flow, so the French researchers decided to test their potential in large mammals (sheep). After one month, the sheep had 15% more effective hearts.

The New Scientist reports more on the details of the study. 5 of the sheep were also given immunosuppressant drugs, and all of the stem cells were tagged with fluorescent markers so their movement through the body could be tracked. There was no sign of rejection by either group of injected sheep. Scientists who commented on the study thought it showed great promise for the treatment of heart disease in humans.

The story has also been reported on ABC News Online (Australian Broadcasting Company), and by the Daily Mail. The Times of Oman and Express India both carry the Reuters wire story.

Fat Derived Stem Cells

Fat Derived Stem Cells

The Pharmaceutical Business Review published a short article on September 12 reporting that researchers from Cytori Therapeutics and the University of California, Los Angeles had used stem cells derived from fat (adipose)to improve heart function in rats. Rats were injected either with fat-derived stem cells or with saline solution. After 12 weeks, the rats that had received the cells had improved heart function. Business Wire gave a more extensive account of this. Both documents are based on a Cytori press release. The results were presented at the third annual International Fat Applied Technology Society conference September 10-13, 2005 in Charlottesville, Virginia. Other research presented by Cytori included research on the differentiation potential of adult stem cells, on the effects of adipose stem cells in dogs and pigs, and on further clinical development.

Stem Cell Research in California

Stem Cell Research in California

In the November 2004 election, California votes approved the creation of a stem cell research institute (the California Institute for Regenerative Medicine) which would allow research on stem cells to take place without the limitations of federal funding. On September 13, 2005, Scientific American reported on the progress of getting the institute operational.

The chair of the institute and the man behind the idea and the voter initiative is Robert Klein, a real estate investment banker. Klein believes that medical research should be considered as fundamental as infrastructure and not be funded on the basis of legislative bills. According to the article, Klein now faces criticism on issues of accountability regarding conflict-of-interest rules and benefits to California residents, among others. The CIRM scientific and medical accountability board has adopted rules laid out by the National Academy of Sciences but is waiting for a 270 day public review process.

Some of the concerns voiced by other scientists are that the public may have too much power and lead to a climate in which factions “attack study results they don’t like and raise money to test their own treatment theories.” Other scientists are concerned that when states set up their own standards for peer review, quality, and ethics instead of relying on those used by the NIH, both scientists and the public become confused about what is acceptable research and what is not.

Klein’s goals include removing administrative and legal barriers to the pace of research. He would like to see a statewide master license on intellectual property that allows biological material to move between institutions, and he would like to approve grants on a three-month basis instead of a nine-month basis.

Research updates 9/9/05-9/11/05

On September 11, 2005, i-newswire reported that European researchers from the Institut Pasteur had isolated muscle stem cells that were more effective in repairing muscles than the stem cells which had been used. The researchers used a new purification procedure which allowed 20,000 stem cells to be used in place of 1 million cultured cells in mice. The researchers are from the EuroStemCell project, which receives funding from the EU and includes laboratories in 24 countries.

The same source also published an article discussing a study in which scientists showed that if some molecules are not in the right location on stem cells, the cells can cause tumors. Stem cells normally divide into two parts, one parent cell maintaining the “stock” of DNA and one daughter cell differentiating into the other cell. When the proteins molecules in the new cell are disrupted, the daughter cell proliferates as a tumor. (This was also published on EurekAlert on 9/4/05.) The original study appears in the September 4 online issue of Nature Genetics.


On September 9, the Wisconsin Technology Network published an article addressing the use of stem cells in drug research. John McNeish of Pfizer's Exploratory Medicinal Sciences area spoke at the University of Wisconsin-Madison. McNeish discussed the advantages of using human stem cells over mouse cells for drug research; cells could be engineered to have specific diseases and drugs tested on those cells, and human cells may respond differently to drugs than mouse cells do, enhancing drug safety. The article also pointed out that European scientists have fewer restrictions on research than American scientists do.

Also on September 9, my.DNA.com posted an article about stem cell research. The article reported on a workshop in Kobe, Japan jointly organized by the Ernst Schering Research Foundation (Berlin, Germany), the Max Planck Society (Munich, Germany) and the RIKEN Center for Developmental Biology (Kobe, Japan). Researchers met in Kobe September 1-3. Research findings included the conversion of human skin cells back into a “multi-potent” stage and the merger of brain cells from mice with embryonic cells, creating hybrid cells which behaved like normal embryonic stem cells. One researcher demonstrated the creation of mice through two egg cell nuclei, rather than a sperm and egg. Other research on reproduction demonstrated that embryonic stem cells can generate into egg cells. It was also suggested that germ stem cells from bone marrow could migrate to human ovaries and create new eggs. Research is also occurring on restoring the insulation of nerves in the brain and on suppressing spinal cord inflammation.

Stem Cells Mutate in the Lab

Stem Cells Mutate Over Time

An article published in the September 4 online issue of Nature Genetics reporting that stem cells mutate under laboratory conditions has received a lot of press.

An article on Newswise reports on a study appearing in the September 4 online edition of Nature Genetics. In the study, researchers from Johns Hopkins Medical Center in the United States and 3 other countries compared "early" and "late" stem cells from 9 of the 22 lines eligible for US federal funding. They found that genetic changes had occurred in the cells as they grew in the laboratory. The researchers examined the "epigenetic marks," methyl groups related to protein production, and found changes in mitochondrial DNA in 2 lines and extra or fewer copies of genetic material in 5 lines. All 9 lines had shifts in the methylation on at least 1 of 3 genes.

Genetic Engineering News gave a detailed report of the same issue. According to this article, the researchers used two GeneChip microarrays to analyze the stem cells' genes as a whole and to specifically examine the mitochondrial genome. They analyzed the exact order of every base (C,T,G, and A molecules) in each stem cell’s mitochondria. This report was based on a press release from Affymetrix, the manufacturer of the microarrays. According to this article, the researchers were able to use the new technology to scan the genetic material in much more detail than could previously be done with a microscope, and to much more quickly sequence the mitochondrial DNA.

This study was also reported on Lifesite.net on September 6. According to that article, "Chakravarti’s research team found that as they were cultured, stem cell lines went through 35 cell divisions and found that 90% showed changes in patterns of methylation – the process in which certain genes in a cell are turned on or off – 22% had mutations in mitochondrial DNA and 50% had major deletions or amplifications in the DNA. Moreover, it was the connection between the particular genetic problems the cells developed and the formation of tumours that was most worrying. "

Reason On-Line gives an account of the basic material researchers used. Some stem cells are frozen after dividing only a few times, while others divide many more times, and researchers compared the early and late ones with each other. Most of the changes found amplify the effect of genes that cause cancer or disable tumor-suppressant genes. One of the consequences of this study is that the stem cells used by federally funded researchers are now more limited, as cells from later lines are likely to have mutated. The article quotes one of the researchers, Dan Arking, as pointing out that cells grown from adult stem cells are even more likely to mutate.

Wisconsin Technology Network gave its version of the same study on September 7, 2005. In this article written for the layperson, researchers from the University of Wisconsin weighed in on the issue, with Dr. Stephen Duncan stating that the mutations had a negative side for stem cell research. On the other hand, Dr. Gabriela Cezar said that the “raw” stem cells themselves are not used in treatment, and it is important to look at the new cells generated by the stem cells. The article concludes with the issue of how this limits the use of the federally funded stem cell lines in both research and treatment.