Increasing supply to meet the demand

Stem cell scientists discover genetic switch to increase supply of stem cells from cord blood for future clinical use

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TORONTO—Most of us who have heard even the slightest explanation of economic theories have at least passing familiarity with the concept of supply and demand—that is, if there’s a lot of something and it’s easily available, demand for it goes down (as well as price). If it’s hard to get your hands on, it becomes more desired and valuable.
It’s probably safe to say that stem cells fall into that latter category. They have much potential for therapeutic use, but even beyond the challenges of getting them to do what we want, there is the challenge of getting sufficient quantities not only for research purposes, but for mass scale-up to the levels required to commercialize and capitalize on any stem cell therapies.
As Canada’s Princess Margaret Cancer Centre of the University Health Network (UHN) notes, they have an inroad on at least one global research team trying to ease that challenge. Specifically, a team of stem cell scientists working internationally, led in Canada by Dr. John Dick and in the Netherlands by Dr. Gerald de Haan, say they have discovered what UHN calls “the switch to harness the power of cord blood and potentially increase the supply of stem cells for cancer patients needing transplantation therapy to fight their disease.”
The researchers published their proof-of-concept findings in July in the journal Cell Stem Cell. Those findings seems to indicate a viable new approach to making more stem cells from cord blood which, as noted by co-principal investigator Dick, a senior scientist at Princess Margaret Cancer Centre, is available through public cord blood banking. Dick is also a professor in the Department of Molecular Genetics at University of Toronto, with which UHN and all its medical institutions are affiliated, and he holds a Canada Research Chair in Stem Cell Biology.
The other co-principal investigator, stem cell scientist de Haan, is scientific co-director of the European Institute for the Biology of Ageing at the University Medical Centre Groningen in the Netherlands.
“Stem cells are rare in cord blood, and often there are not enough present in a typical collection to be useful for human transplantation. The goal is to find ways to make more of them and enable more patients to make use of blood stem cell therapy,” noted Dick. “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.”
As it stands now, when patients need stem cell transplants, they are matched to an adult donor with a compatible immune system through international registry services. As with any other transplant situation, however, thousands upon thousands of patients globally are unable to get stem cell transplants they need to fight blood cancers like leukemia because there is no donor match.
Of course, another challenge is the number of donors, something the research of Dick and de Haan can’t address. As noted on the EuroStemCell website, where the issue of risks of stem cell treatment of leukemia are addressed—key among them infections and graft-versus-host disease—the organization explains: “Researchers and doctors are investigating ways to improve current transplantation approaches in order to address these limitations. Another challenge is the shortage of donors, and several organizations are working to increase the number of volunteers in donor registries.”
“About 40,000 people receive stem cell transplants each year, but that represents only about one-third of the patients who require this therapy,” Dick pointed out. “That’s why there is a big push in research to explore cord blood as a source, because it is readily available and increases the opportunity to find tissue matches. The key is to expand stem cells from cord blood to make many more samples available to meet this need, and we’re making progress.”
The research teams of Dick and de Haan are, naturally, far from being the first set of researchers to explore the idea of expanding the quantity of stem cells found in cord blood, but they say they do take a novel approach compared to other work in this area. As they explain, when a stem cell divides it makes many progenitor cells immediately downstream that retain key properties of being able to develop into every one of the 10 mature blood cell types; however, these cells subsequently lose the ability to self-renew that all true stem cells possess.
In the lab, by analyzing mouse and human models of blood development, the teams discovered that the microRNA known as mirR-125a is a genetic switch that is normally on in stem cells and controls self-renewal—this normally gets turned 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 Dick.
Stem cells were first discovered in Toronto in 1961 at the Princess Margaret by Drs. James Till and the late Ernest McCulloch, notes UHN—a discovery that “launched a new field of science and formed the basis of all stem cell research that continues to this day.”

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