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About SickKids

April 27, 2009

Stem cells are going green to study autism

Scientists have developed a new technique to quickly identify stem cells with the goal of fast-tracking medical advancements

(Toronto) - Recent breakthroughs in stem cell research have enabled scientists to induce human skin cells to become stem cells, but these stem cells are hard to find. A research team led by The Hospital for Sick Children (SickKids) has developed a method to efficiently identify human stem cells by turning them fluorescent green. The findings are reported in the April 26 advance online edition of Nature Methods.

"This new technique is simple and reliable and allows us to isolate the best stem cells quickly,” says Dr. James Ellis, principal investigator of the study, SickKids Senior Scientist and Associate Professor of Molecular Genetics at the University of Toronto. "This has exciting implications for studying disease and for future cell therapies."

The new development is on the heels of the recent discovery that human skin cells can be induced or "reprogrammed" to become stem cells (induced pluripotent stem cells or iPS cells). After two to four weeks, stem cell colonies emerge, but it has been challenging to find the best ones to study. Using their new method, the SickKids scientists can simply look for the green colonies to find the most suitable ones. These colonies can then be expanded into useful stem cell lines that can produce any cell type in the body.

To test the new technique, they isolated stem cells to study a form of autism called Rett syndrome. They turned them green by using a virus to transfer the Green Fluorescent Protein gene into human and mouse skin cells.

"We designed the green gene to be off in skin cells, but to turn on when they are reprogrammed to become stem cells," says Dr. Akitsu Hotta, lead author of the study and a post-doctoral Fellow from Japan (funded by SickKids Restracomp Award). "We can then pick the best stem cell colonies that glow green under the microscope and expand them to study human disease." To make the system even more efficient, researchers also included a drug-resistance gene alongside the green gene. This ensures only the best stem cells grow in the presence of the drug and the rest of the cells are unable to survive.

After showing the system worked on normal mouse and human cells, it was used to isolate stem cells from both a patient and a mouse with Rett syndrome, an autism spectrum disorder that affects girls. It is caused by a mutation in the MECP2 gene and affects nerve cell maturation in the brain. The researchers showed they could make nerve cells from the patient stem cells. These cells can be used in the future to investigate how nerve cells mature in patients with autism, signal to their neighbours and to find drugs to correct the defects.

Ellis says this new screening method has even further applications. He explains that with some diseases or injuries, mature cells made from stem cells could be used for transplantation therapy, but there is a risk that any stem cells left in the culture could form tumours in the recipient.

"We noticed that tumours did not form if we transferred pure populations of mature cells into mice, but if green stem cells were also present, tumours were quickly established," says Ellis, Co-Director of The Ontario Human iPS Cell Facility located at SickKids, where researchers have used this new technique to isolate iPS cells from 10 patients with diseases such as cystic fibrosis. "The green gene effectively signals the presence of tumour-forming stem cells, and these could be removed before transplantation is performed."

Future research initiatives would be to include a gene that would kill stem cells that could potentially form tumours. The researchers are currently modifying their method so that the green cells also come equipped with this type of suicide gene.

The research was supported by the Ontario Ministry of Research and Innovation, the Canadian Institutes of Health Research, the Stem Cell Network, SickKids Foundation and the International Rett Syndrome Foundation and SickKids Restracomp Award.

The Research Training Competition (RESTRACOMP) provides stipend funding for graduate students pursuing a Master’s or Doctoral degree in the biomedical sciences, and research fellows who have obtained a PhD, MD or equivalent, and are pursuing at least two years of research training. The competition runs biannually (deadlines are usually April 15 and October 15 of each year). Applicants are evaluated by a committee on a number of criteria, including academic performance, publication activity, and other research, academic and professional development activities.

The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, is Canada’s most research-intensive hospital and the largest centre dedicated to improving children’s health in the country. As innovators in child health, SickKids improves the health of children by integrating care, research and teaching. Our mission is to provide the best in complex and specialized care by creating scientific and clinical advancements, sharing our knowledge and expertise and championing the development of an accessible, comprehensive and sustainable child health system. For more information, please visit www.sickkids.ca. SickKids is committed to healthier children for a better world.

For more information, please contact:

Matet Nebres
The Hospital for Sick Children
Phone: 416-813-6380
email: matet.nebres@sickkids.ca

Suzanne Gold
The Hospital for Sick Children
Phone: 416-813-7654 ext. 2059
email: suzanne.gold@sickkids.ca