Researchers from the University of Toronto and Kyoto University recently met in Japan to forge a revolutionary partnership on stem cell research. The collaboration has Toronto researchers joining forces with the world-renowned stem cell researcher Dr. Shinya Yamanaka.
For many years, scientists have studied embryonic stem cells (ES cells) due to their potential to differentiate into virtually any cell of the body. In 2007, Dr. Shinya Yamanaka and his team made a revolutionary discovery. Using normal human skin cells, Dr. Yamanaka reprogrammed them to an embryonic-like form. These new cells are known as induced pluripotent stem cells (iPS cells) and are believed to have the same properties as ES cells.
“Together, we’ll share reagents, ideas and protocols to accelerate research and translate the research into clinical outcomes,” says Dr. Bill Stanford, associate director at the University of Toronto’s Institute for Biomaterials and Biomedical Engineering and co-scientific director of the Ontario iPS Cell Facility. “This is quite important because this research has significant clinical potential, which is not 20 years down the line but, at least for some therapeutics, maybe 10 years.”
Dr. Stanford recently returned from a symposium in Kyoto, Japan. The scientist said that Dr. Yamanaka was amazed at the research Ontario scientists are doing. The collaboration will be a two-way partnership. For example, Kyoto researchers could provide new technologies to produce iPS cells and Toronto scientists may offer novel ways of differentiating these cells.
This partnership adds to Canada and Ontario’s growing list of research accomplishments in the field of stem cell biology. Since the 1960s, it was the work done by pioneers James Till and Ernest McCulloch of the Ontario Cancer Institute in Toronto that sparked the field of stem cell biology. Since then, Canada continues to rank in the top six countries internationally for its ongoing leadership in stem cell research. In a recent industry briefing, it was noted that nearly one third of all stem cell researchers are from Ontario.
Since Till and McCulloch, stem cell research has branched out into many discrete and exciting fields of study. Dr. Stanford and his team work on modelling human diseases with genetically altered mice. “Now, we can model human diseases with actual human sample by generating iPS cell lines from patients and differentiating these cells to the affected cell types,” explains Stanford. The scientists hope to uncover underlying causes of the disease and develop drug screens to discover effective drug treatments.
The two major advantages of iPS cells are due to the way they form. No fetal embryonic tissue is required for the development of iPS cells—all the work is done in the Petri dish. Therefore, the ethical dilemma that was one of the major barriers in stem cell research is no longer a factor. Furthermore, by using reprogrammed cells from the original patient, the chance that the patient will undergo immunological rejection is unlikely.
Although iPS cells can differentiate into any cell type, “initially research will concentrate on treating and understanding paediatric conditions and developmental disorders because they can be easily modelled,” Stanford says. These include conditions such as cystic fibrosis (CF) or autism.
“With iPS cells, researchers at Sick Kids are trying to develop a proper protocol to differentiate these cells into lung epithelium cells so they can study Cystic Fibrosis iPS cells and perform drug screens,” says Stanford. This research would greatly help the lives of the one in 3,600 Canadian children that have CF.
In addition to paediatric conditions, iPS cells can be easily differentiated into neurons. Dr. James Ellis, associate professor in the Department of Medical Genetics at U of T and co-scientific director of the Ontario iPS cell facility, studies neurological disorders and will be involved in this research collaboration.
Dr. Ellis and his team study Rett syndrome, a neurodegenerative childhood disease, similar to autism. It affects one out of every 10,000 baby girls. “With iPS technology we can differentiate the cells into neurons and study the disease with quite ease,” says Ellis. He adds that this would normally be very difficult because you cannot extract nerve cells from living individuals’ brains.
This technology also gives scientists the ability to better model neurological diseases like Rett syndrome because mice and humans are not exactly equivalent. “Humans have certain higher cognitive abilities that can’t be translated into mouse models,” says Ellis.
Dr. Ellis will also be involved in the partnership between Toronto and Kyoto. “Since we have so many patients in Ontario, we offer a large diversity of patient samples on which models and treatments can be made from,” explains Ellis. “iPS cells also allow us to test drugs using a Petri dish and not making patients go through the treatments to see what works and what doesn’t.”
Although not in the immediate future, Ellis and Stanford agree that this partnership will spark the possibility of cell based therapy and transplantation. “Imagine a patient who suffers from heart disease, with iPS cells we will be able to repair the heart with the patients’ skin cells,” says Ellis. However, he adds, iPS cells need to be rendered safe before this application can be successful. It would require the use of retroviruses, which could enable cells to proliferate uncontrollably—a characteristic seen in cancer.
“Eventually, cell based therapies will be possible and patient specific iPS cells would be possible and that is one of the exciting things of these cells and this partnership,” says Stanford.
