HKU Bulletin August 2010 (Vol. 11 No. 3)

10 The University of Hong Kong Bulletin 11 August 2010 The new medical possibilities promised by stem cells are flagged with two important considerations: where should the stem cells come from, and what is the most efficient way to put them to work in patients? The Faculty of Dentistry may have some answers. Researchers there are extracting stem cells from teeth to grow jawbone, which could eventually help patients whose healing is compromised by radiation therapy, diabetes or heavy smoking. They are also collaborating with the University of Freiburg in Germany to develop one-step dental stem cell transplantation, which would reduce contamination risks by doing all the extraction and transplantation in the operating theatre. “Every person has baby teeth and permanent teeth and sometimes young patients need to extract their wisdom teeth or other teeth,” says Cheung Lim-kwong, Chair Professor of Oral and Maxillofacial Surgery. “It’s more comfortable for patients to get stem cells from their teeth than from bone marrow.” The stem cells come from inside the pulp of the tooth and in the membrane of the ligament around the teeth. Although the volume of dental stem cells is not as great as that from bone marrow, the researchers have shown that they are at least as effective. They manipulated dental stem cells to grow into jawbone and transplanted them into rabbits with jawbone defects. The result was a regeneration of bone, offering hope to those who are disfigured due to jawbone loss. The researchers are also keen to explore the possibilities of one-step stem cell transplantation. Everything from stem cell extraction to stem cell differentiation into the desired type of bone or tissue to transplantation into the patient, is done within the operating theatre. “The University of Freiburg started doing this three years ago and we’re collaborating with them and getting advice. We’re trying to learn from them and build on their findings. We want to do a basic science approach to confirm it’s working so we’ve started some animal studies with this,” Professor Cheung said. A further boost to the Faculty’s stem cell research is coming from Visiting Research Professor Herman Cheung from the University of Miami, who has successfully tested dental stem cells in cardiac repair. Professor Cheung visits the Faculty this summer and will return several times over the next couple of years to collaborate with our researchers. Professor Herman Cheung (left) and Professor Cheung Lim-kwong. SAVE YOUR wisdom teeth The Faculty of Dentistry is testing teeth as a source of stem cells and investigating a faster, more efficient way to transplant these cells. HELPING AILING hearts to beat Our researchers have been at the forefront in using stem cells to repair sick and damaged hearts. Stem cell therapies are old hat to Professor Tse Hung-fat, William M.W. Mong Professor in Cardiology of the Department of Medicine. He led a team that conducted the first human trial of bone marrow stem cells to treat patients with severe coronary heart disease in 2001, and has been focused ever since on finding the best stem cell therapies for patients. “Despite advances in medical and surgical therapies, a large number of patients with cardiovascular disease remain severely symptomatic and have poor clinical outcomes,” he says. “Regenerative medicines are going to play an ever more prominent role in these cases, but we do have some significant challenges to overcome first.” The bone marrow trial showed that stem cell therapy could be effective in patients who otherwise had irreversible damage to their hearts. The cells were injected into the heart through a catheter and more than half of the patients showed clinical improvement, such as better cardiac function and enhanced development of new blood vessels. The treatment was also shown to be safe. Initial trials involved 36 patients in total and a larger-scale study is now underway with about 100 patients. However, bone marrow-derived stem cells are not a perfect solution because they are limited in their ability to generate new cells in the heart muscle. This is where recent developments in stem cell research show promise. Professor Tse and his team have demonstrated in laboratory testing that induced pluripotent stem cells (iPSCs) – derived from adult cells – could more effectively develop into cardiac cells than bone marrow stem cells. Tests have supported this using small animals and the scientists are now investigating the response in pigs. “We want to make sure it works and that we don’t get any harmful effects before we move to human trials,” he says. “It’s still a long road and also expensive, because every patient would have to generate their own iPSCs” to avoid problems of rejection. But the researchers are also looking into an alternative stem cell source that could be applied to all patients and would not have a rejection risk. Another stream of research has used stem cell and gene therapies to develop a bioartificial pacemaker. This involves injecting cells into the heart, rather than implanting an electronic pacemaker as is done at present. Tests on pigs with arrhythmia have so far shown good results and the scientists are monitoring them to see if the bioartificial pacemaker can work well over the long term. Professor Tse says HKU is unique in enabling its scientists to follow through their research from laboratory bench to hospital bedside. “A lot of other institutions around the world have good people doing basic research and good people doing clinical research, but the two aren’t linked as such. We’ve streamlined the whole process so we can actually go through from basic research to human trial,” he says. That capability has been supported by the University’s investments in stem cell research, including a $10 million allocation for the cardiac repair programme and funding for core facilities that enable research on human stem cells. Professor Tse Hung-fat Cover Story