When Dr. Jeff Biernaskie and his University of Calgary Skin Regeneration Team set to work to build better skin grafts with stem cells, they wanted to talk to those with the most at stake: burn injury survivors.
“I came into this without the experience of working with patients,” says Dr. Biernaskie, an assistant professor in stem cell biology. “So I got together with a burn physician Dr. Vincent Gabriel, to ask, ‘What are the deficiencies somebody faces when they’ve had a burn and a skin graft?’ We wanted to ask them, ’What would make your quality of life better?’”
The team is conducting patient surveys to find out how burn survivors feel about their grafts, what their expectations are and how their priorities change over time. They are also asking how burn survivors feel about stem cell transplants to regenerate dermal tissue — the thick layer under the epidermis that contains blood capillaries, nerve endings, sweat glands and hair follicles.
“It’s a different kind of pain in the beginning than it is later — often chronic itch is more problematic than pain in the long term” says Dr. Biernaskie. “A year later, you also may have limitations on mobility because of scarring. So you may have a very different perspective on what you’d be willing to accept in terms of the risks — for example, the risk of aberrant growth, which might require additional surgeries — or the potential of failure of the stem cell transplant.
“These are real concerns, but by talking to patients living with skin grafts, our goal is to identify their most critical deficiencies and then design therapies to address those, so that any potential shortcomings are outweighed by the potential gains in function.”
The survey findings will help guide the Skin Regeneration Team as they move closer to conducting clinical trials on human patients. Right now, they are transplanting human dermal stem cells into skin-grafted mice, and seeing positive results.
“We’re seeing the cells respond in the appropriate ways, spreading out across the area of the graft. What’s impressive to me is to see that the cells actually move up into the skin graft and interact with the epidermal cells, repopulating parts of the graft that may have been deficient. By regenerating new dermis, we hope that we can positively affect the function of the overlying epidermis, which otherwise is typically quite fragile after split thickness skin grafting. The cells are starting to secrete a lot of the collagens and the other factors needed to remodel that skin.”
They hope to be testing the stem cell transplants in larger animals such as pigs, which have skin more similar to that of humans, within two years.
“We want to look at the innervation (interaction with the nerves) of the graft, vascularity of the graft, as well as the histological (anatomical) functions of the graft. All these things need to be looked at to see how much of an impact we’re having.”
Ultimately, the goal is to use the burn patient’s own skin cells to create millions of dermal stem cells that can be used for transplant, an autologous procedure that limits the risk of rejection and the need for immunosuppression drugs.
The team has cell biologists working on characterization of adult dermal stem cells — drawing them out of skin from an adult human and understanding the biology behind them. They are also working with bioengineers to explore how to expand the cells using bioreactors to rapidly generate the large numbers of cells needed.
“We want to develop an autologous cell-based therapy to regenerate the dermis — that’s really our goal,” says Dr. Biernaskie. “I’m optimistic. We can readily get the cells out from a patient, we’re able to grow them up from relatively small numbers of starting cells and we’re working on different matrices and scaffolds to improve survival and integration once they’re grafted in.”
He is even more optimistic about using stem cells to treat chronic skin wounds.
“Think of elderly patients with chronic wounds who are having their dressing changed every three days or so. That’s a lot of nursing costs, and bandages. And it’s grueling for the patients. If you could take a biopsy, grow up a few hundred millions of cells, and then repopulate a chronic wound in order to get it to close and re-epithelialize, that would really have an impact on quality of life — and on the associated health care costs. That’s something we’re going to look at.”
The work being done by the Skin Regeneration Team is supported by Alberta Innovates Health Solutions and the Calgary Firefighters Burn Treatment Society.
Current care for burn injuries:
The current standard care for deep burns is split thickness skin grafting, which involves taking epidermis (outer) and part of the dermis (inner) layers of skin from elsewhere on the patient’s body and then grafting it onto the burn site. Short term, the process is painful. Long term, additional grafts are often needed and the transplanted skin tends to scar, which can severely limit mobility, and are extremely fragile, leading to frequent wounds. Also, the grafted skin is devoid of dermal appendages, such as sweat glands and hair follicles.
The potential stem cell solution:
Researchers hope stem cells drawn from the patient’s healthy skin can be coaxed to create millions of precursor cells than can be seeded into the dermal layer of the burn wound to generate new skin tissue that will fully integrate with the epidermal layer and help to grow new dermal appendages. The hope is that this regenerated tissue will be less prone to scarring and bleeding and provide better overall function.