Expert Perspective by Nicole Ehrhart, VMD, MS, Diplomate ACVS
Tell us about your involvement with Limb Preservation Foundation.
Nicole: In August 2015, I became the inaugural holder of the Wilkins University Chair at Colorado State University, named in honor of Dr. Ross M. Wilkins, who founded the LPF in 1986. Known officially as the “Ross M. Wilkins Limb Preservation University Chair in Musculoskeletal Biology and Oncology” at Colorado State University, my chair position was funded by a $3 million endowment from Dr. Wilkins that supports research in limb preservation and musculoskeletal oncology and biology at CSU. Although I am the first holder of the Wilkins University Chair, I will not be the last – Dr. Wilkins’ endowment ensures that this position will live on in perpetuity as long as the University exists, and the chair will be bestowed upon future scholars involved in limb preservation studies.
Prior to receiving the Wilkins University Chair, I was also a board member for the LPF for __ years.
What is your research agenda?
Nicole: I have been actively involved in limb preservation research, regenerative medicine, tissue engineering and sarcoma research for the last 25 years. My lab’s work helps to prevent limb loss in people and animals whose extremities are threatened by cancer, infection, or trauma. We utilize surgical and bone-grafting techniques and biologic therapies to carry out these studies. Stem cell therapy is a key component of our tissue engineering studies to regenerate affected bones and muscles.
What are stem cells and stem cell therapy?
Nicole: A lot of different ideas come to mind when people hear the phrase “stem cell.” Probably the most controversial is the idea of fetal stem cells; these are cells that are taken from a human fetus or any animal species before they’re born. Those cells have very special properties: embryonic (or fetal) stem cells can turn into almost any kind of tissue in the body. But what people often don’t realize is that adults have stem cells, too. In fact, every single tissue in the adult body has stem cells in it, though there are fewer stem cells in our bodies in adulthood.
What are they? Well, stem cells are the repair cells of the body. Essentially, adult stem cells lie dormant in the body for long, long periods of time until an injury happens or growth is needed, and suddenly they’re activated. They begin to divide. They mobilize and can home to sites of injuries, and then they secrete very special chemicals, like growth factors. Stem cells essentially “gather the troops,” if you will; they prompt the signals that cause the rest of the body’s healing response to begin, resulting in the healing of the tissue.
There are stem cells in every tissue of our bodies – liver, heart, brain, everywhere. The area of interest that I’ve had for several years is the stem cells that are found in our connective tissues, like muscles, tendons, fat, and bones. These are called mesenchymal stem cells, or MSCs, and they’re only found in adults. My interest in MSCs is what launched my exploration into regenerating muscle.
How can stem cells improve degenerative diseases and conditions found in adults?
Nicole: When people were starting to get interested in adult stem cells, there was this thought that stem cells were like a magic bullet that could heal, repair or reverse conditions that happen in our bodies, either because of wear and tear, like what happens in aging, or from injury and illness.
What’s happened is that scientists have gotten savvier about what these cells can and can’t do. There are still a lot of questions, but it turns out that the hype about stem cells was a little bit ahead of the science. And so, for probably the first 10 years of stem cell use in regenerative medicine, it was the Wild West: stem cells were being tried for just about any disease you could think of, from Parkinson’s disease, to blindness, to congenital conditions, to arthritis. The thought was that stem cells were these cells that could transform into any tissue, and if we inject them at the site of an injury, or in the vein so they could circulate around the body, then arrive at the site and heal the injury or repair what was wrong.
While stem cells do indeed circulate and travel to sites of tissue injury – in fact, that’s one of the cool aspects of stem cells – now we know that if they are injected into a vein or joint very few of the cells survive for very long, and even fewer of them differentiate into the tissue that was damaged.
Instead, the primary way stem cells do their job is to secrete a whole bunch of good signals that coordinate the body’s healing response. And in doing so, they can decrease chronic inflammation and help repair or restore function in areas of the body that have been diseased or injured.
Where is stem cell therapy headed in the future?
Nicole: Stem cell therapies have been difficult to perfect because there is so much variation in stem cells from person to person. The number of stem cells in one person’s muscles, for example, may be very different than another person. Stem cell number depends on a million factors, like how much fat tissue a person has, their lifestyle habits, like whether they’re smokers or not, or their age. There are currently no FDA approved stem cell therapies because there isn’t enough evidence – with a single kind of stem cell therapy in a single disease – to prove that the therapies make a difference. Scientists haven’t been able to define the most effective dose, or the best practices for stem cell “therapy,” because the ways we purify and deliver stem cells to an individual have been so variable in the history of research.
But it’s, important we don’t throw the baby out with the bathwater. While it’s been difficult to get consistent numbers and consistent biologic activity from person to person among stem cells, we do know that the secretions from stem cells are important; they’re the primary reason why stem cells work in very controlled circumstances to regenerate tissue or heal.
In my lab, we are studying those secretions and categorizing what’s in them to determine what is the “magic juice” in stem cells? And it turns out that a major player in the secretions is this tiny particle called an extracellular vesicle. A vesicle is just what it sounds like a very, very small vessel, and in this case, the vessel is surrounded by a cell membrane that can protect a certain component, or “cargo,” in that vesicle, shielding it from the body that will break it down too quickly, such that it can’t arrive at the site of injury.
To be continued…
Tune back for my next blog post in August to learn about regenerative medicine 2.0 and the cutting-edge approach my lab is pioneering: extracellular vesicle therapy for sarcopenia (muscle loss).