The recent discovery that human skin cells can be induced to become stem cells has exciting implications for studying disease and for future cell therapies. However, very few stem cells are normally found in these experiments. So, how do we overcome this problem? Within our lab at the Hospital for Sick Children we developed a method to identify human stem cells by turning them green. The method, reported in Nature Methods (April 26 online doi:10.1038/nmeth.1325; print forthcoming May 2009) quickly isolates the best stem cells so that we can then pick the best stem cell colonies that glow green under the microscope and expand them to study human disease in a petri dish.
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. Rett Syndrome is caused by a mutation in the MECP2 gene and affects nerve cell maturation in the brain. Our research showed we 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, how they signal to their neighbours and to find drugs to correct the defects.
As a further application of this technique, these mature cell types made from iPS cells could be used for transplantation therapy with some diseases or injuries, 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 then tumours were quickly established. In other words, the green reporter gene monitored the presence of tumour-forming stem cells prior to transplantation and could be used to remove them.
-- Akitsu Hotta and James Ellis, Hospital for Sick Children