Speedy recovery: How a serendipitous discovery could improve the quality of life for people with diabetes
When we get injured – whether it is a papercut, a scraped knee, or a serious car accident – trillions of cells in our body work together to help us heal from that injury. But for people living with chronic diseases such as type 2 diabetes, this healing process doesn't happen so easily.
"Most of the time, when you're young and active and healthy, the tissues within your body can repair or regenerate themselves very quickly and very easily after an injury," says Dr. Adam Johnston, principal investigator of the Johnston Lab. "For example, if you cut your finger, it might bleed for a little while, then start to scab over, and then eventually heal to the point where there is only a small scar left. But for people with chronic diseases like type 2 diabetes, this unfortunately isn't the case."
Type 2 diabetes is a complex disease that occurs when the body cannot produce enough insulin (a hormone that helps control the amount of sugar in our blood) or does not properly use the insulin it produces. This means people with diabetes often have higher levels of sugar in their blood, which can lead to risks of serious health complications such as stroke, heart attack, cardiovascular disease, cognitive dysfunction, motor dysfunction, and more.
"Type 2 diabetes affects more than 3 million Canadians and is what we call a 'multisystem dysfunction,'" says Dr. Johnston. "This basically means that it affects nearly every system in the body, from the nervous system to the immune system to the cardiovascular system. When we're recovering from an injury, all of these systems need to work together to help our tissues repair themselves, but if any system isn't working or isn't performing at its best – which is often the case for people living with diabetes – then it makes it very difficult to heal from even minor injuries."
Understanding and addressing the health risks
As a result, one of the biggest complications associated with diabetes is developing wounds that do not heal or return time and time again, called chronic nonhealing wounds. For example, people living with type 2 diabetes may develop pressure ulcers if they sit or stand for too long. These ulcers damage the skin and tissue underneath and cause skin discoloration, inflammation, and severe pain. And if such wounds do not heal over time, they run the risk of getting infected, which could lead to amputation.
"Chronic nonhealing wounds are the number one reason for amputations in Canada – other than traumatic injuries, for example from a car accident – and cost our health care system approximately $500 million annually," Dr. Johnston explains. "On top of that, the five-year mortality rates among people who undergo an amputation are incredibly high, sometimes more than 50%, meaning there's a strong chance patients may not survive for longer than five years after their surgery."
For Dr. Johnston, these statistics were a call to action.
"We don't quite know why tissues lose their ability to heal and regenerate when you have a chronic disease like type 2 diabetes," Dr. Johnston says, "which is why we need to do more research to understand the human biology better and find answers to this question. When it comes down to it, that's what my team and I are aiming to do with our research: find answers that will, in time, help improve and speed up the recovery of chronic nonhealing wounds and ultimately improve the quality of life for people living with type 2 diabetes."
Exploring the power of Schwann cells
As part of his work, Dr. Johnston is exploring the potential of a particular type of cell called Schwann cells to help accelerate the healing process of nonhealing wounds.
"Typically, Schwann cells are found throughout our peripheral nervous system, and they basically act as 'helper cells' for our nerves," he explains. "We have billions of nerve cells in our body, which help us to walk and talk and move. But when we puncture or injure our skin, we also injure the nerve cells underneath. This is where the Schwann cells come in. When our nerves are injured, the Schwann cells secrete factors that help the nerve repair itself."
For many years, it was believed that Schwann cells only supported the healing of nerve cells and did not influence the healing of dermal cells (or skin cells). But in 2016 while completing his post-doctoral fellowship, Dr. Johnston discovered that these mighty cells may hold more power than scientists originally thought.
"At the time, I was doing research on mice to investigate the function of different dermal cell types during skin wound repair," he explains. "But in these experiments, we noticed that when the skin – and, by extension, the nerves – of mice were injured, some of the Schwann cells kind of climbed out of the nerve cells and mixed in with the dermal cells to help the skin repair itself as well. So, they were sort of playing two healing roles at once."
Before Dr. Johnston's discovery, this phenomenon hadn't been known to happen before. Ultimately, it suggested that Schwann cells could help with more than just healing our nerves; they could help with skin cell recovery and tissue repair as well.
"In science, we tend to use this word all the time: serendipity," Dr. Johnston says. "At the time, we were doing research to find answers to a completely different question – this wasn't on our radar at all. But that basic, fundamental research I was doing eventually snowballed and led me to where I am today."
Finding treatments to improve patient quality of life
More than six years later, Dr. Johnston and his team are building on that discovery to understand if Schwann cells can in fact play a role in healing chronic nonhealing wounds and how that could lead to a treatment for people living with type 2 diabetes.
"Our work right now is pre-clinical research, meaning we're not at the point where we can safely test on humans," Dr. Johnston says. "Eventually though, we hope to find answers that could lead to real-life, human applications and treatments."
For their current research, Dr. Johnston and his team are using models of mice that have had type 2 diabetes since they were just four weeks old. By damaging the skin of the mice, the team can track how the skin cells heal, how quickly they heal, and what the healing process looks like over time, from the moment of injury to the final recovery. They are also looking closely into the role of Schwann cells during this process and exploring whether transplanting healthy Schwann cells into the skin cells of the mice could help speed up the recovery time.
Dr. Johnston hopes this work will deepen our collective understanding of Schwann cells and skin cell biology, which may ultimately lead to the development of a treatment or therapy for chronic nonhealing wounds.
"The goal with basic, fundamental science is always to have the 'bench to bedside' consideration in the back of your mind," he says. "In other words, we want to think about how the work we're doing in the lab will help patients in the real world. This often means collaborating with experts in other disciplines, like bioengineering and clinical research, to make sure our work can make a real difference. After all, type 2 diabetes is a complex, life-altering disease, and finding treatments will require an interdisciplinary approach. My work is just one piece of the larger puzzle, but over time, I hope it will set the foundation to find solutions that improve the quality of life of all Canadians living with diabetes."