blood stem cells
Some time ago we blogged about the research into leukemia stem cells done by a team at the Institute for Research in Immunology and Cancer (IRIC) of Université de Montréal.…
Some time ago we blogged about the research into leukemia stem cells done by a team at the Institute for Research in Immunology and Cancer (IRIC) of Université de Montréal. This week, IRIC announced it is moving forward.
In collaboration with the Centre for Commercialization of Regenerative Medicine (CCRM), IRIC Commercialization of Research (IRICoR), has launched ExCellThera, a spin-off company that will improve the process of cord blood stem cell transplantation for patients with acute myeloid leukemia (AML). Click here to discover how stem cells are being used to treat leukemia and other blood disorders on our Toward Treatments page.
“We are excited to be working with CCRM to launch this new IRICoR spin-off company located in Montréal, which includes novel stem cell-expanding molecules that were initially identified and funded at IRIC via an early-stage investment from IRICoR,” Michel Bouvier, CEO of IRICoR, said in the IRIC press release.
ExCellThera is based on novel proprietary intellectual property related to the expansion of stem cells developed by two members of our Foundation’s Science Leadership Council: Dr. Guy Sauvageau, Scientific Director & CEO of IRIC, and Dr. Peter Zandstra, Professor at Institute of Biomaterials and Biomedical Engineering, University of Toronto and Chief Scientific Officer of CCRM.
A Phase I and II clinical trial, designed to test the ability of ExCellThera’s stem cell expansion approach, will begin this year at the Maisonneuve-Rosement Hospital in Montreal, and will grow to include Sainte-Justine Hospital and other centres in the near future. The trial will involve up to 25 patients suffering from AML.
Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine.…
Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine. Where do they see things going? What are they excited about? For today’s instalment, we interviewed Dr. Denis-Claude Roy, Director of the Centre de recherche de l’Hôpital Maisonneuve-Rosemont and a full professor at the Université de Montréal. Dr. Roy is Chief Executive Officer of CellCAN Regenerative Medicine and Cell Therapy Network. Asked about what he sees developing in the field of stem cells and regenerative medicine he provided the following highlights of his work and others.
In our work with blood-based cancers like leukemia and lymphoma, we have developed a protocol for stem cell transplantation for people who don’t have a matched donor. We are able to do mismatched stem cell transplants, or what’s called haploidentical stem cell transplantation. This means that in place of being fully compatible (with the donor cells), a patient can be 50% compatible and still get a transplant.
Normally (such a transplant) would kill the patient, but we’ve developed a strategy to eliminate the cells that cause Graft Versus Host Disease (GVHD) and attack the patient. GVHD is probably the biggest problem associated with stem cell transplantation. Instead of having the patient develop GVHD or treating the patient with drugs to prevent it from occurring, we treat the cells in the lab and eliminate those that cause GVHD. So, we’re able to do stem cell transplants without immune suppression and the patient won’t have to take immuno-suppressor drugs for the rest of their lives.
We’re very excited about this. Our first study included 19 patients and we have had extremely good results. The patients had few infections and low relapse rates. A second study on another 23 patients, part of an international study, is currently led by our centre. To date, patients are again doing very well.
We’re also starting a clinical trial using a molecule called UM171 that was developed by Dr. Guy Sauvageau (Université de Montréal) to expand umbilical cord blood stem cells while maintaining their properties. Right now, donated umbilical cords have too few cells to treat adults. One donation provides enough cells to treat a child, but not enough for a normal size adult. Currently for an adult, we have to use two donations and that presents immune issues and is very expensive. We want to ramp up the number of stem cells from umbilical cord donations for those patients that have a match but not enough cells. We can grow the cells in the lab to have enough for the transplant.
This will allow us to select from our larger pool of umbilical cord blood donations and therefore improve the match, which should result in decreasing the number of complications associated with transplants and make it possible for more people to get them. This could also accelerate engraftment, shortening the time for the cells to engraft, which would decrease risk associated with the procedure.
The the use of stem cells in cardiac treatments is also starting to gather momentum. Dr. Duncan Stewart (University of Ottawa) has a trial (using genetically modified stems to repair heart damage) that is going very well. I am also working with Dr. Nicolas Noiseux (Université de Montréal) on activating stem cells before they are infused into the heart. He is studying a number of molecules to activate the cells before they are injected. The idea is to repair the hearts of patients who have poor cardiac function.
We will also be starting a trial using cells from the immune system to target leukemia. They are specific, acting like missiles, which will select and kill leukemia cells. Dr Claude Perreault (Université de Montréal) is developing a series of new targets. A new clinical trial is likely to start in the Fall.
The world of haematology research is mourning the loss of one of its giants, Prof. Donald Metcalf, who has died at the age of 85.…
The world of haematology research is mourning the loss of one of its giants, Prof. Donald Metcalf, who has died at the age of 85.
A native of New South Wales, Australia, Prof. Metcalf received a Carden Fellowship in cancer research at Melbourne’s Walter and Eliza Hall Institute of Medical Research in 1954.
Starting from an interest in leukemia, Prof. Metcalf focused his research on blood cell production. Following the findings of Canada’s Drs. James Till and Ernest McCulloch, who first isolated stem cells in 1961, Prof. Metcalf and his team discovered colony-stimulating factors (CSFs), hormones that regulate white blood cell production.
The discovery of CSFs has had a significant impact on the recovery of cancer patients after chemotherapy. The injection of CSFs can reduce susceptibility to life-threatening infections by increasing the number of blood cells responsible for fighting those infections.
“Over the past 20 years, more than 20 million cancer patients have been treated with CSFs and, as a result, have been given the best possible chance of beating their cancer. There can be no greater legacy for a medical researcher.” according to a tribute by Prof. Douglas Hilton, Director of Walter and Eliza Hall Institute Of Medical Research, and Profs. Warren Alexander and Nicos Nicola, Heads of Institute’s Division of Cancer and Haematology.
Despite many opportunities across the world, Prof. Metcalf spent 60 years as a Carden Fellow at the Institute, even after his official retirement in 1996. He received several Australian and international awards for his work. Among these were the Companion of the Order of Australia (1993), the Albert Lasker Award for Clinical Medical Research (1993) and the Robert Koch Prize (1998).
Diagnosed with pancreatic cancer in August, Prof. Metcalf, also known as “the father of modern haematology,” performed his last experiment in October and died surrounded by his family on Monday.
The unveiling of a clinical trial to test the use of genetically enhanced stem cells to rebuild badly damaged hearts captured major media attention in early September.…
The unveiling of a clinical trial to test the use of genetically enhanced stem cells to rebuild badly damaged hearts captured major media attention in early September.
CBC News, the Sun and Postmedia newspapers all called the trial “groundbreaking” and gave it prominent play. CTV called it a “world-first clinical trial.” The Globe and Mail coverage was somewhat more restrained but went into fine detail to explain how the patient’s own blood stem cells are enhanced with a gene called endothelial nitric oxide synthase (eNOS) that is then infused into the heart at the site of the damage.
It didn’t hurt that the Ottawa Hospital Research Institute, where Principal Investigator Dr. Duncan Stewart is CEO and Scientific Director, was able to put a gentle human face on complicated science by presenting Patient No. 1. Sixty-eight-year-old Harriet Garrow of Cornwall, Ontario suffered a major, heart-stopping myocardial infarction in July. Holding hands with her husband Peter Garrow, she was amiable, articulate and authentic. Reporting the news Sept. 10, the Aboriginal Peoples Television Network highlighted her heritage, headlining its story “Mohawk woman in centre of ground breaking medical treatment.”
This is a double-blind study – meaning neither the investigators nor the 100 participants in Ottawa, Montreal and Toronto will know who received the souped-up stem cells or the comparative controls of ordinary stem cells or placebos until after the results are in. That doesn’t matter to Mrs. Garrow, who, at the very least, is getting the best of current cardiac care. “I am thrilled to play a part in this research that could help people like me in the future and, who knows, perhaps even my children and grandchildren,” she said in the OHRI’s media release.
A decade of work
Investigators will start analyzing the results after Patient No. 100 has been enrolled and treated – more than two years from now. By that time, Dr. Stewart will have put 10 years into the project he originally started at St. Michael’s Hospital in Toronto.
But things could happen quickly after that.
“Most major medical centres in Canada and the United States have the capacity to do this kind of cell manufacturing, “ says Dr. Stewart. “So, if we allow ourselves to dream a bit, that this really is a very positive trial with major improvements, I think it could be adopted quite quickly.”
The implications – in terms of thousands of lives that could be saved and millions of dollars in health care costs avoided – are immense. About 70,000 Canadians have heart attacks every year. Dr. Stewart estimates that about one-third of those, around 23,000, suffer damage severe enough to require this level of intervention.
“This segment of the infarct population is one that’s going to cost an awful lot of money because before they die they are going to develop heart failure. They’re going to be having multiple prolonged hospital admissions and require implantation of defibrillators and are going to have all kinds of other treatments that cost the system a lot of money.”
Other trials using ordinary stem cells have shown some positive effect on repairing heart tissue, but nothing that would spark widespread change in how heart attack patients are treated. The difference here is these stem cells have rejuvenated with eNOS to do a more effective repair job.
“It’s always been our view that getting the most robust therapy requires some manipulation of the cells, particularly when you’re using the patient’s own cells,” says Dr. Stewart. “The cells are the same age as the patient, which is usually 60 or 70 years old, and they have been exposed to the same factors that produced heart disease in the first place. We know they don’t work well. But if we can recover the activity of these cells we’re going to get more benefit.”
It all depends, of course, on The Big If: If it works.
Given the rigorous controls and criteria included in the clinical trial, the answer should be obvious within three years.
Just a few weeks ago, when most of us were focused on soaking up the last rays of summer sun, a new development in how stem cells renew themselves didn’t see much light of day, media-wise.…
Just a few weeks ago, when most of us were focused on soaking up the last rays of summer sun, a new development in how stem cells renew themselves didn’t see much light of day, media-wise. It should have.
Dr. Norman Iscove, a senior scientist at the Princess Margaret Cancer Centre whose pedigree traces back to pioneering bone marrow transplant efforts led by Dr. Ernest McCulloch in 1970, has quietly opened up a new frontier. One that has huge implications for cancer.
After years of work, the lion’s share of which was done by postdoctoral fellow Dr. Catherine Frelin, Dr. Iscove’s team was able to show that a gene called GATA3 plays a key role in the rate at which blood stem cells renew themselves. They found that by tinkering with it they could get stem cells to up their self-renewal rate and make many more stem cells.
In a practical sense, this discovery could help address the shortage of stem cells for transplantation. If, by interfering with GATA3, scientists could ramp up stem cell production, doctors could then do more bone marrow transplants and save more lives.
That kind of application, however, is likely a long way off. The GATA3 findings, published in Nature Immunology, are based on work with mice – not people. “I can’t even begin to predict it,” says Dr. Iscove. “Before knowing whether it’s playing the same role in human stem cell self-renewal, it’s too soon to say.”
But there is something more fundamental to consider here. Something that has much larger implications down the road.
“We know that stem cells can be preprogrammed in terms of longevity,” says Dr. Iscove. “There are stem cells we can purify completely that will reconstitute almost permanently. But there are others that sometime after eight weeks will begin to fail and the grafts will regress. Both of them are genuine stem cells. Both of them are capable of pumping out billions of cells every day. But one is preprogrammed to quit. We now think that GATA3 is a key player in reprogramming the permanent stem cell to become a transient stem cell.”
Dr. Iscove believes that understanding the differences between permanent and transient stem cells is absolutely central to understanding how cancer develops.
“Cancer cells have permanence in terms of growth,” he says. “They don’t quit. They keep going. That’s why they’re dangerous.”
Viewed this way, the potential application of the GATA3 discovery is far beyond simply improving the ability to scale up the production of progenitor cells. It could be the key to shutting down cancer stem cells.
“It’s part of the puzzle of understanding permanence in stem cell renewal,” says Dr. Iscove. “How is that done and how do you break it?” The answer won’t be found anytime soon.
As said, Dr. Iscove has opened up a frontier. He and others must now explore it.
That, at the very least, is exciting.