Wound Healing

Aug 2015
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Jeff Biernaskie

Researchers ask burn survivors: ‘What would make life better?’

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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.…

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.

[Find out more about stem cells and wound healing here.]

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Apr 2014
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Thinking outside the heart

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Stem cell derived mini-heart can pump blood through sluggish veins

A U.S.-based researcher has come up with what she believes is a stem cell solution for sluggish blood flow that could knock the socks off the current standard of care.…

Stem cell derived mini-heart can pump blood through sluggish veins

A U.S.-based researcher has come up with what she believes is a stem cell solution for sluggish blood flow that could knock the socks off the current standard of care.

“Compression stockings have been used since antiquity,” says Dr. Narine Sarvazyan, a researcher at George Washington University in Washington, DC. “So we really haven’t made much progress in treating chronic venous insufficiency.”

The condition is common, affecting between 20-30% of people over the age of 50. It can be particularly distressing for people with diabetes, causing non-healing ulcers to form on their legs or ankles. It can also affect people who are paralyzed and those recovering from surgery.

Dr. Sarvazyan’s solution is to implant a “mini-heart” made of stem cell derived heart muscle cells called cardiomyocytes at the site where the blood is stagnating.  The cells form a cuff that wraps around the problem vein while rhythmically contracting and releasing to move the blood along. You can see a short video of how it works here.

The invention of the mini-heart has caused quite a stir online.  It has been picked up by the Huffington Post, Science Daily and Business Standard

So far, Dr. Sarvazyan has only created “in vitro” (Petri dish) versions of the mini-hearts in her lab. Her next step, after finalizing the design, will be to move to animal tests with rats and, ultimately, pigs. In a best-case scenario, she hopes to begin clinical trials with people after about two years.

The advantage is the mini-hearts can be tailor-made from stem cells extracted from the patient’s own fatty tissue so that there will be no danger of rejection and little risk of inflammation.

“It’s a very different application,” says Dr. Sarvazyan. “Most people who work with these cardiomyocytes have a goal of repairing cardiac muscles. That is pretty much where everyone is aiming.  But the idea came into my mind that we can use the same tissue and actually use it in different locations much more easily. You don’t have to have that much structured muscle. It doesn’t have to have much force. It’s easier to vascularize because it’s smaller.”

Dr. Sarvazyan outlines the advantages in a paper called Thinking Outside the Heart, published, in the Journal of Cardiovascular Pharmacology and Therapeutics.

“So far I don’t see any downsides,” she told Stem Cell NewsDesk.  “Of course, nature is much smarter than us. It’s possible when we put it in animals, something may happen that we could not predict.  I can’t say for sure that it will work — we definitely need to test it.”

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Apr 2014
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Jeff Biernaskie

The bald truth

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The Daily Mail, one of the feistier UK tabloid papers, recently blasted this headline across its health pages:

Have scientists discovered a cure for BALDNESS? 

The Daily Mail, one of the feistier UK tabloid papers, recently blasted this headline across its health pages:

Have scientists discovered a cure for BALDNESS? 

Would that it were true.  According to the Huffington Post, 80 million Americans “suffer from hair loss.” For Canada, then, about 8 million people are hiding hairless heads under their hockey toques. (Full disclosure: I am one of them.)

The article is based on research conducted at the Perelman School of Medicine at the University of Pennsylvania and published in Nature.  In a nutshell, Dr. Xiaowei “George” Xu, converted human skin cells into induced pluripotent stem cells to produce large quantities of epithelial stem cells, which are normally found in hair follicles. When transferred to mice, the cells created “recognizable” shafts of hair.

How recognizable is debatable.  But still, this represents an advance.

However, Dr. Xu urged caution: “We have solved one major problem, the epithelial component of the hair follicle. We need to figure out a way to also make new dermal papillae cells, and no one has figured that part out yet.”

Dr. Jeff Biernaskie (pictured at right) of the University of Calgary agrees. Any cure for baldness, he says, would have to incorporate re-invigorating dermal cell function.

“The problem is the dysfunction of these inductive dermal cells. Essentially, they either start providing wrong signals or they die off or atrophy. So the therapy that needs to be championed is actually restoring the function of dermal papillae cells. You need to revitalize those cells to restore hair growth.”

Dr. Biernaskie is not focused on finding new ways for follicles to grow on the heads of bald people. His lab is trying to decode how stem cells work to rebuild skin tissue for burn survivors, or people with chronic non-healing ulcers.

The reality, however, is that any stem cell researcher who could come up with a cure for hair loss would have the cosmetics industry pounding down their door. There would be billions of dollars to be made from such discovery — enough to set a researcher up for life, allowing him or her focus on tackling problems that can’t be solved with a wig or expensive hair transplants. “To be honest, I don’t know what could happen,” says Dr. Biernaskie, “but probably you would be financially set.”

Meanwhile, he and researchers around the world are trying to figure out the dermis puzzle.

“The reason we are working on dermis is that, while it’s a key target for restoring hair growth for conditions like androgenetic alopecia (male pattern baldness), it’s also critical for maintaining proper epidermal cell function and overall skin health. So if you can understand how to regenerate the epidermis and the dermis without forming scars and potentially generating new appendages (like follicles and glands) within that skin, that’s sort of a Holy Grail.”

Until then, the search continues. As does being bald.

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