Stem cell research updates

By Dr. Ananya Mandal, MDMar 3 2011

Stem cells must be used with caution

Two studies have been published this Wednesday in the journal Nature that show that work remains before so-called induced pluripotent stem (iPS) cells are ready for use in laboratory studies or clinical therapies. These iPS cells are body cells that are programmed to unwind back into an embryonic state.  Like embryonic stem cells, they have potential to develop into any other type of cell in the body. However researchers are showing that these cells do not reprogram perfectly.

A team at the Salk Institute showed that iPS cells hold on to “memory” of their past identity. These papers have shown that the processes through which iPS cells are reprogrammed also can create significant abnormalities in the DNA itself. Such reprogramming errors could affect the cells' usefulness in the future, the authors wrote.

Co-author Dr. Andras Nagy of the Samuel Lunenfeld Research Institute of Mount Sinai Hospital in Toronto said, “These mutations could alter the properties of the stem cells, affecting their applications in studying degenerative conditions and screening for drugs to treat diseases.” Nagy said that the discovery of the mutations also had “important implications” for the use of iPS cells in medical therapies. Researcher Kun Zhang of the University of San Diego, a co-author on the other paper called these abnormalities “permanent genome scars”. The teams suggested that iPS cells should undergo careful genetic screening before they are used.

Stem cells to fight the immune system

In a separate study researchers at Stanford University reported a new method to prevent immune system rejection in human embryonic stem cells transplanted in mice.  Their results, which suggest there may be options that avoid the side effects of traditional immunosuppressant drugs, were published Thursday in the journal Cell Stem Cell.

One of the greatest problems in stem cell research is rejection by the host patient’s immune system. The new technique tested by scientists in the US involves a short course of treatment with three specific immune system-dampening drugs. Known as “co-stimulatory receptor blocking agents”, the drugs target key elements of the immune system called T-cells and “teach” them to accept the donor cells.

Researchers at Stanford University in California tried the treatment out on mice with embryonic stem cells implanted into their leg muscles. Untreated mice rejected the cells within 21 days, while those given continuous treatment with traditional immunosuppressant drugs lasted around eight days longer before mounting an immune response. But the transplanted cells continued to flourish in mice that received just four treatments with the blocking agents.

Dr Joseph Wu, who led the research said, “We are very excited about the clinical potential of this finding. The immunological issue is one of the most important biological problems to solve, in my opinion. Clinicians need to make sure there is no tumor formation, and also that the cells are not rejected.”

Stem cell research suffers from paper work burdens

According to a leading research laboratory Australia’s stem cell research is being stifled by red tape. The lab at Sydney IVF says it has been forced to shelve viable projects because of the long and tedious approvals process. Stem cell research is tightly governed by federal laws introduced first in 2002. Since then just 12 projects have been granted licenses needed for scientists to begin their work. Sydney IVF Stem Cells was one to receive most approvals.

Strategy and regulation manager Dr Julia Schaft said, “We could not achieve what we achieved ... without the licenses and the permissive legislative framework in Australia, and so in that respect we are very fortunate…But all this comes at a price, and a license application process is long and tedious. The Act, for example, was put into action in 2002. Yet even though Sydney IVF immediately applied for these licenses the first was not handed out ... until April 2004…So while we are working in a very fast-paced scientific environment, and if we want to adapt our research we are facing sometimes significant delays caused by this system.”

Oversight of the research is performed by the National Health and Medical Research Council (NHMRC), and existing stem cell-based projects must be re-submitted every time an extension is sought or researchers shift their focus. Dr Schaft said there was a period in 2009 where consideration of some projects was on hold for six months.

“More than once we have dismissed a viable scientific option because we did not have the resources to deal with the administrative burden,” she added. She also mentioned that smaller companies or research groups could find themselves unable to justify the extra time and resources, and divert their efforts elsewhere.

The federal government in December announced it was reviewing the laws governing stem cell research, and a period of public consultation is now under way. Dr Megan Munsie from the Australian Stem Cell Centre said the oversight systems was functioning well but could be better. “With some refinements (it) could be improved,” she said.