With so much news about the continued roller coaster of the COVID-19 pandemic, it is easy to forget that other areas of health research are continuing to surge ahead. But the latest Order of Canada announcement makes it clear that there are a lot of reasons for Canadians to feel hopeful.
One hundred and thirty five Canadians were appointed to the Order of Canada at the end of 2021 in recognition of extraordinary service with the aim of bettering the nation. Among the list of health researchers appointed as members are Gregory Marchildon, a health-care policy researcher; Lynn Posluns, founder of the Women’s Brain Health Initiative; and Peter Zandstra, director of the new School of Biomedical Engineering at the University of British Columbia.
Zandstra has been at the forefront of stem cell research for years. Healthing spoke with him to about his work, his goal of treating cancer without chemotherapy and how science can tackle fake news.
This interview has been edited for length and clarity.
You started your career with an undergraduate degree in chemical engineering from McGill University. What drew you to biomedical engineering?
McGill had a minor in biotechnology, which I thought was a really nice opportunity to start to see how traditional chemical engineering skills can be applied to problems in health. Chemical engineering typically had applications in things like oil and gas, or pulp and paper, or environmental things, but the whole emerging area of biotechnology was really starting to be quite hot at that time in the “olden days.” And so a couple of courses in that area got me really turned on to how bioengineering and biomedical engineering could combine with engineering design to solve problems in health.
You were a co-author of a 2001 publication that has been credited with coining the term “stem cell bioengineering.” Can you explain what that means?
Stem cell bio engineering is the application of engineering principles to problems in stem cell biology. It’s been quite an exciting area because we’ve seen a growth in this field over the last 20 years or so. Now there’s an annual stem cell engineering conference, there are many labs across the world working on many different problems, from How do we engineer molecular circuits inside cells to control stem cell fate? to How do we engineer the environment around cells so that we can control their development? to more practical problems like how we manufacture cells and scale [the manufacturing process] so that we can produce living cells as therapeutics for devastating diseases. It’s been really fun to watch the growth of this field and its impacts both here in Canada, where we’re really going to lead in the area, and internationally, where there’s a lot of really fun contributions from others.
There’s a lot of research going on in the Zandstra lab. What are you working on now?
We’re quite focused on the blood forming system, which traditionally has two types of clinical applications. One is using umbilical cord blood stem cells — those are blood stem cells derived [or developed] from the [umbilical] cord blood that’s normally discarded from a patient at birth. It’s enriched in blood stem cells, and we’ve been trying to figure out how to grow those to larger numbers so they can be used as replacements for stem cell transplantation. Typically, when you do stem cell transplantation, you have to have a [donor] match and we may or may not have enough cells to treat patients. If we can grow those cells, then that would solve that problem.
The other thing we work on, which is really something we’ve focused on over the last five years or so, is generating T cells [a type of white blood cell that makes up an important part of the immune system] from pluripotent stem cells. These types of cells are now being used as immunotherapies against cancer. We’re engineering those cells to express specific cancer targeting [markers] or proteins on their surface, and then helping to see whether those cells can seek and destroy cancer cells in our body after they have been manufactured and transplanted.
The umbilical cord issue is so interesting. One of the criticisms about storing your baby’s cord blood is that there may not be enough stem cells if, say, 20 years down the road, your child needs them to treat a blood disorder. So you’re saying that you’re trying to address that problem now, by actually trying to make more stem cells?
Exactly. We’ve shown we can we can grow blood stem cells derived from umbilical cord blood about 10 times more than was originally there. So that makes that cell population quite useful for larger patients or potential other applications.
Editor’s note: If you’re interested in reading more about using stem cells to treat blood cancer and the agony of finding a match, read What it feels like: Sister’s stem cells keep boy alive
How do you get a stem cell to grow into those kinds of regenerative cells?
It’s important to remember that there are different types of stem cells. There are pluripotent stem cells, which are cells that are able to give rise to all the cells in our bodies. These cells can be derived either as embryonic stem cells, which are derived normally from discarded embryos, or through new technology called induced pluripotent stem cells. Any cell in our body that has a nucleus, [the area of the cell that contains DNA,] can be reprogrammed to be a pluripotent stem cell. [Called an induced pluripotent stem cell.]
[Pluripotent stem cells] are easier to grow in large numbers, but you need to differentiate [or develop] them into different cell types or tissues before you can think about using it for drug screening or perhaps as a therapy.
The other type of stem cell is a somatic stem cell. This is a stem cell that would be in your body right now — adult stem cells is another word for it. Blood-forming stem cells are one example of that, but there are other ones. There might be liver stem cells, or neural [brain] stem cells or other cells. Those cells are typically restricted in their developmental capacity to a specific tissue or lineage and in some cases, those cells could be used directly as therapeutics without differentiating. The challenge there is how we grow more of them [called proliferation], or how you generate or manipulate them inside their bodies.
So for each different cell type we have different challenges that we’re facing, some of which involve controlling the environmental differentiation, and then some of them involve controlling what we call self-renewal, which is really the proliferation of those cells without allowing them to differentiate.
How are you looking into using stem cells to help the immune system fight cancer?
In this case, we’re using pluripotent stem cells to make T cells, which are the effector cells of our immune system. There are different types of T cells. One type of T cell is called a CD8+T cell, and this is a T cell that can engage with cancer cells to kill them. What we’re doing is engineering the T cells so they express these anti-cancer molecules on their surface, and then when we transplant them, the hope is that they go seek and destroy the cancer cells in the body.
Is the goal to be able to treat cancer without chemotherapy?
Chemotherapy is one way that people try to reduce tumour masses. We’re looking right now at whether cellular immunotherapies can be used as a more precise way of doing that. So when you use chemotherapy, you can imagine that you kill all dividing cells in the body, which is quite an aggressive therapy. Whereas immunotherapy or engineered T cells fall into the category of precision medicine, because they have targeting molecules on the surface that, theoretically anyways, only target the cancer cells because those are the only cells expressing those specific targets.
Are there any misconceptions of stem cell research that you would like to address?
Stem cell research is very much an area that has a lot of promise. And while we’ve had some significant advances in our ability to use stem cells in therapies, it is still very much an area where more research is being done. I think one of the areas that causes a lot of concern to scientists is where you have hype and exploitation of patients by saying specific types of therapies will cure disease. These so-called stem cell clinics have been a big area of controversy and risk where people will claim that certain types of stem cell therapies work very well for diseases and [will] charge a lot of money for people to travel to different places in Canada or across the world, really, for these therapies.
I’m part of an organization called the International Society for Stem Cell Research that has a website called A Closer Look at Stem Cells, that talks about the types of questions people should ask before engaging in different experimental therapies.
So you’re saying it’s more of a relationship between the doctor and the patient versus a clinic simply saying, We can give you this and it will cure whatever condition you have.
Yeah, and then making sure that the science is backed in the therapy. Stem cells have been well developed for therapies against blood diseases and there are a number of new areas moving forward that are very exciting in treating diseases such as Parkinson’s and others with stem cell derived therapies. But at the same time, they are still very much under experimental testing in clinical trials, and we need to make sure that we go through those tests and they become properly validated before we start offering them more broadly to patients.
We live in the era of misinformation and fake news, where cutting-edge technology has had loud opposition. Where do you feel scientists and researchers fit into the broader conversation with non-scientists?
That’s a great question. I think science outreach and science communication is an increasingly important responsibility for scientists. It’s also a challenge. It takes a lot of practice and effort to learn how to communicate complex ideas in a way that is both accurate and allows the nuances of that information to be appreciated. I think having scientists as part of the conversation, having opportunities such as this [interview] where we can work with people to help bring forward scientific stories, where maybe we could have more training programs for scientists and graduate students to learn how to communicate, are all important things. Certainly, this is something we’re trying to do with the University of British Columbia and Michael Smith Laboratories, where science communication and science outreach is an important priority.
You are the director of the new School of Biomedical Engineering at the University of British Columbia. What is the goal of the program?
This is really where we’re trying to bring together engineering and biology and technology at a fundamental level to advance some of these ideas, including stem cells, but also other areas such as lipid nano-particle delivery and machine learning and AI. I think there’s a great opportunity when you remove the silos between different scientific disciplines to accelerate the discovery of new technologies.
That’s something that I think I’ve benefited from in the past; I was able to work in between the chemical engineering and a hematology lab. What we’re trying to do is sort of formalize that environment where there’s less barriers between different scientific disciplines. We’re pretty excited about that.