A study led by Dr. Mick Bhatia at McMaster University shows that a readily available drug that induces fat cell production in bone marrow also suppresses leukemia while promoting the production of healthy blood cells.…
A study led by Dr. Mick Bhatia at McMaster University shows that a readily available drug that induces fat cell production in bone marrow also suppresses leukemia while promoting the production of healthy blood cells.
“The focus of chemotherapy and existing standard-of-care is on killing cancer cells but instead we took a completely different approach which changes the environment the cancer cells live in,” Dr. Bhatia, Director and Senior Scientist with McMaster’s Stem Cell and Cancer Research Institute, explained in a press. The study published in the journal Nature Cell Biology.
Increasing fat cells in the bone marrow creates an environment that favors the growth of healthy blood cells and blocks out leukemic cells. The team targeted a single cell type in one tissue and had positive results when tested in mice.
Dr. Bhatia believes that there is immediate translational potential with minimal side effects as the drug can be given in a much lower dose and with a shorter duration than in its intended use for diabetes treatment. In an interview with CBC, Dr. Bhatia said that the team is looking to move to clinical trials on humans within two to three years.
International stem cell scientists, led in Canada by Dr. John Dick and in the Netherlands by Dr. Gerald de Haan, have found the switch to harness the power of cord blood and potentially increase the supply of stem cells for cancer patients needing transplants.…
International stem cell scientists, led in Canada by Dr. John Dick and in the Netherlands by Dr. Gerald de Haan, have found the switch to harness the power of cord blood and potentially increase the supply of stem cells for cancer patients needing transplants.
The findings, published today in Cell Stem Cell, could provide a way to make more stem cells from cord blood, which is increasingly available through public cord blood banking.
“Stem cells are rare in cord blood and often there are not enough present in a typical collection to be useful for human transplantation,” says Dr. Dick, Senior Scientist, Princess Margaret Cancer Centre, University Health Network (UHN), in a media release.
“Our discovery shows a method that could be harnessed over the long term into a clinical therapy and we could take advantage of cord blood being collected in various public banks that are now growing across the country.”
The Dick-de Haan teams found that when a stem cell divides it makes progenitor cells that retain key properties of being able to develop into any one of the 10 mature blood cell types, but they have lost the stem cell’s key ability to self-renew.
Working with mice and human models of blood development, the teams identified microRNA (mirR-125a), a genetic switch that is normally on in stem cells and controls self-renewal, gets switched off in the progenitor cells.
“Our work shows that if we artificially throw the switch on in those downstream cells, we can endow them with stemness and they basically become stem cells and can be maintained over the long term,” says Dr. Dick.
This is just the latest discovery by Dr. Dick. He isolated a human blood stem cell in its purest form and was the first to identify cancer stem cells in leukemia and colon cancer.
Dr. de Haan is Scientific Co-Director, European Institute for the Biology of Ageing, University Medical Centre Groningen, the Netherlands.
Dr. Dick talks about their research at here.
Dr. Allen Eaves, a member of the Canadian Stem Cell Foundation’s Board of Directors and a founding Till & McCulloch Leadership Circle member, is being appointed to the Order of British Columbia — the province’s highest form of recognition.…
Dr. Allen Eaves, a member of the Canadian Stem Cell Foundation’s Board of Directors and a founding Till & McCulloch Leadership Circle member, is being appointed to the Order of British Columbia — the province’s highest form of recognition.
An internationally respected leukemia researcher and clinician, Dr. Eaves is the founder and owner of Vancouver’s STEMCELL Technologies Inc., Canada’s largest biotech company. He co-founded the Terry Fox Laboratory and served as its director for 25 years as well as heading the BC Cancer Agency for 18 years, developing one of the first bone marrow transplant programs in the world.
Called the “cell-made man” by BC media, Dr. Eaves began STEMCELL in 1993 with a staff of eight. He now employs more than 800 people. STEMCELL develops specialty cell culture media, cell separation products and ancillary reagents for life science research and delivers them to scientists around the world. In 2015 STEMCELL was named Life Sciences Company of the Year by LifeSciences BC.
Dr. Eaves has a strong incentive to continue his efforts, telling BCBusiness in 2013 that “I want t to cure cancer. That’s the motivation,” he said. “It’s all about curing some of these diseases, wiping them off the face of the earth.”
The investiture will take place July 26 in Victoria. To read more about Dr. Eaves, click here.
Dr. Sheila Singh is driven to know why one Christopher died when the other thrived.
About 20 years ago, while in her third year of a residency rotation and working in pediatric neurosurgery at Toronto’s SickKids Hospital, Dr.…
Dr. Sheila Singh is driven to know why one Christopher died when the other thrived.
About 20 years ago, while in her third year of a residency rotation and working in pediatric neurosurgery at Toronto’s SickKids Hospital, Dr. Singh was assigned two five-year-old boys. Both were named Christopher. Both had medulloblastoma, the most common kind of childhood brain tumour.
“I took care of them hour to hour, day to day. They both got the same surgery, the same chemo, the same radiation. In all clinical ways, the tumours were identical. One Christopher did very well and was cured. The other died. I had this huge epiphany in that moment: I realized that even if I did neurosurgery for the rest of my life, I would never figure out why one Christopher survived and one died.”
Dr. Singh realized that, along with being a brain surgeon, she needed to understand the molecular and cellular biology of brain tumours. She entered the Surgeon Scientist Program at the University of Toronto where, while still a PhD student working in Dr. Peter Dirks’ lab, she was lead author on the 2004 Nature paper that identified human brain tumour initiating cells.
Since returning to her native Hamilton in 2007, Dr. Singh has worked as a pediatric neurosurgeon at McMaster Children’s Hospital while doing complementary research with Mac’s Stem Cell and Cancer Research Institute.
“There’s a bridge that connects the Children’s Hospital on the fourth floor to where my lab is and I go back and forth. When I have a whole week of clinical work, where I’m covering emergency operations on call and doing clinics, you see everything that the children go through. When I go back to the lab, I’m filled with clinical questions: Why did this happen to this child? It’s gratifying to have this research lab where I can bring questions to a useful end.”
In her research, Dr. Singh uses preclinical mouse models of brain cancer to improve treatments for her patients.
“We’ve developed ways of adapting the therapies that we use on children for immune-deficient mice. We transplant the human tumours into the mice and treat them with the exact same chemotherapy or radiation protocols that the children get. So I can profile — in a personalized medicine way — what’s going on with each child’s tumour. That’s the aim of these preclinical models: to model what’s going on in the patient in a faster, higher-throughput way. I’m hoping that one day we will have a model that will allow us to feed back to the patient: ‘You have this cell population that’s going to escape radiation, so you are going to need this added drug to help you with your therapy.’”
Another approach is to take a sample of the child’s tumour cells and test the use of various compounds to defeat them. “We have a compound screening and drug screening program at the Institute. So we can take the patient’s cells and screen them against libraries of thousands and thousands of compounds. Theoretically, we can find something that will work better as a therapy.”
Regardless of the approach, hers is the opposite of ivory tower, research-for-research-sake activity. It is all patient-driven.
“You see a lot of things in pediatric neurosurgery and all of them — good and bad — inspire my research. And every person who works with me has a direct connection to the ‘Why?’ of research. Very often patients and their families will come for a tour of the lab and my people get to meet them. There is a real connection. People in my lab work twice as hard because they have that direct motivation.”
On a personal level, doing research has made her a more patient person.
“Surgeons — we’re activists. We like to say, ‘OK, we’ll take that tumour out and you’ll feel better.’ But research requires long-term thinking. Research forces me to be patient, have vision and plan in the long term. I’m not a patient person, but I’m learning.”
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.
While Canada’s athletes continue to pile up medals at the Winter Olympics in Sochi and prove their prowess on ice and snow, our stem cell scientists are demonstrating that they too are the best in the world.…
While Canada’s athletes continue to pile up medals at the Winter Olympics in Sochi and prove their prowess on ice and snow, our stem cell scientists are demonstrating that they too are the best in the world.
On the same day that 1,000-metre speed skater Denny Morrison came off the bench (courtesy of team mate Gilmore Junio surrendering his spot) to win silver, Dr. John Dick’s team at the University Health Network in Toronto showed the world what the origins of leukemia look like, publishing their findings in the prestigious journal Nature. That news comes hard on the heels of fellow UHN researcher Dr. Gordon Keller’s discovery of a key regulator that controls the formation of blood-forming stem cells, published in the top-tier Cell.
Both papers represent advances in how we understand and may someday treat disease. Without wanting to sound over-the-top patriotic, both prove that, as a nation, we continue to do outstanding work in the field founded by two Canadians — Drs. James Till and Ernest McCulloch — more than 50 years ago.
Essentially, Dr. Dick has identified a “pre-leukemic stem cell” that appears to initiate acute myeloid leukemia (AML) and, because chemotherapy doesn’t eradicate it, allows the disease to come back. Readers of this blog will recall that Dr. Dick was the first in the world to identify cancer stem cells. He proved that just as stem cells produce millions of specialized cells to build and repair tissues and organs (while also renewing themselves), cancer stem cells drive the production of millions of tumour cells (while also replicating themselves).
“What we found is the first normal cell, the cell of origin, that actually sets off the of cascade events, which is going to ultimately lead to leukemia,” Dr. Dick explains in the UHN video above. “So, one of the direct implications and benefits of our findings is that we should be able to detect leukemia before it arises. And, by identifying patients like that earlier, we should be able to follow them and introduce therapy an earlier stage.”
It should be pointed out that this is very early-stage work. To have application in cancer prevention or care, scientists must find a drug that can target a mutation in the gene called DNMT3 that causes these pre-leukemic stem cells to develop. Such a drug would have to be rigorously tested, something that could take years. But it’s still a very important advance.
“What’s John’s given us is something to go after before the disease gets out of hand,” says Dr. Mick Bhatia, Director of the McMaster Cancer and Stem Cell Biology Research Institute. “That’s a huge gift. It’s like stories about the unicorn. He has identified it, now we have to figure out how to capture it. What we have to grapple with is: ‘Are these pre-leukemic cells targetable?’ ‘Can you diagnose them?’ and ‘Can you shut them down before they become leukemic?'”
In his discovery, Dr. Keller, Director of the McEwen Centre for Regenerative Medicine, identified a key regulator controlling the formation of blood-forming stem cells in the early embryo. He focused on retinoic acid, which is produced from vitamin A and is vital in growth. His team demonstrated that the retinoic acid signalling pathway is critical to making blood-forming stem cells. In experiments with mice, the researchers found that blocking the pathway blocked the formation of blood-making stem cells. Activating it pathway set off an upsurge of blood-forming stem cells.
“Our findings have identified a critical regulator for directing pluripotent stem cells to make blood-forming stem cells, bringing us one step closer to our goal of developing a new and unlimited source of these stem cells for transplantation for the treatment of different blood cell diseases,” says Dr. Keller in Medical News Today.
This discovery is also early-stage work, but also very important, says Dr. Bhatia.
“He is capturing a pathway that is critical for when the first blood stem cell is born and how it makes copies of itself — the self-renewal process. That is going to be instrumental in how we move forward clinically.”
While neither finding is a cure for cancer, both are important steps forward on the path to get there. To push the Olympics analogy a bit further, this is like winning a preliminary competition that allows you compete in the medal round.
Except this is not a game and in this medal round, the prize is much more precious than gold.