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Research With Bite: Researchers are studying how stem cells extracted from discarded teeth could one day improve the lives of people SCI.

Imagine a world in which patients with spinal-cord injuries (SCI) carry their own cure. Within days, a week or a month of their injury, they could be inoculated with self-derived stem cells that could improve grip strength, enhance hand function and even help restore the ability to walk.

Researchers at Craig Center for Regenerative Research at Craig Hospital in Englewood, Colo., aim to bring that science fiction to reality in the not-so-distant future.

"I firmly believe we'll have a major breakthrough in cure research in the next decade. We want a complete cure, if possible," says Leslie Morse, DO, co-founder of the research center and endowed director of SCI research at Craig Hospital. The world-renowned rehabilitation hospital specializes in the neuro-rehabilitation and research for patients with SCI and traumatic brain injury.

Until 1998, scientists believed the central nervous system was a fixed system incapable of regeneration, unlike skin cells or muscle cells, for instance.

Science has since proven that neural cells can, indeed, regenerate, which brings new hope to an array of patients, including those with SCI, multiple sclerosis, traumatic brain injuries or stroke-induced damage.

"The field of rehabilitation medicine is such a rapidly changing and advancing field," Morse says. "It's the most exciting field of medicine these days. There are so many things happening in rehabilitation that it's almost in the domain of science fiction. I'm really excited and hopeful we'll see changes soon."

Stem cells are building block cells that can self-replicate and differentiate into many cell types. Morse's study looks at a source of embryonic stem cells most people still carry: their teeth.

"Dental pulp stem cells are intriguing because every healthy tooth has a large number of your stem cells," she says. "Because of their embryonic origin, these cells can be driven into neural-type cells."

While stem cell research dates back to the early 1960s, the discovery of dental pulp as a source didn't occur until 2000.

"There's been a lot of focus on obtaining stem cells from elsewhere, like bone marrow, which is a painful procedure, and they haven't been effective in recovery for spinal-cord injuries," Morse says.

Dental pulp, however, is relatively plentiful and relatively easy to access from any healthy teeth: discarded baby teeth, extracted wisdom teeth or, potentially, during root canal procedures.

"Dental pulp is exciting," Morse says.

Partnering with Ricardo Battaglino, PhD, at the University of Colorado-Denver, Craig's researchers are using stem cells from extracted wisdom teeth. When injected in rats with bruised spinal cords, the most common form of spinal injury after trauma, results have been promising. From the time of injury and injection to eight weeks post-injury, the rats are displaying improved limb motor function, the lab reports.

"We know that the dental pulp stem cells do improve strength in paralyzed rats," Morse says. "Now we want to make sure the cells stay in the cord and don't go into other tissues or cause tumors."

The next step will be to determine if there is similar improvement if the injection is done one week post-injury.

"After spinal-cord injury, the hope is that we would be able to obtain dental pulp from an individual and be in a position to inject the necessary cells a month or six weeks after injury," Morse says.

A patient might sacrifice a single tooth or its pulp in favor of a lifetime of mobility.

"The hope of any intervention is that it will be effective in acute or chronic injuries," Morse says.

Preserving Baby Teeth

Baby teeth, those bits we naturally shed and pass off to the tooth fairy, could also serve as a bottomless resource.

"I find it intriguing that a young person losing baby teeth rapidly may serve as a donor for an older family member," Morse says. "The other really amazing thing about baby teeth, they divide very rapidly, much more quickly than older individuals. Pulp from adult teeth still have tremendous capacity for the tissues to basically produce stem cells and expand, but baby teeth do it very quickly."

While those old baby teeth saved in a box in the attic are dried up and fairly useless at this point, newly fallen teeth could provide fresh pulp for preservation and future use.

"Pulp dries up, but like we've had a campaign toward preserving umbilical cord blood, we should have a move toward saving and banking baby teeth or any teeth. As soon as a tooth is shed, it needs to be obtained and processed to preserve that pulp," Morse says.

Currently, the National Dental Pulp Laboratory in Marlborough, Mass., provides such a service. Morse's research team also has developed a biorepository of cryopreserved cells. They have developed protocols for pulp isolation, dental pulp stem cell culture and neuro-induction of stem cells, as well as protocols for cell characterization.

"There are dentists who have programs to provide home kits to take a baby tooth that is lost and send it back to have pulp extracted and cells banked," Morse says. "It's really important we get more people banking those."

Initially, Craig researchers saw those cells being used for family members, but they might also be appropriate for anyone. Multiple studies have shown that stem cells derived from dental pulp are less likely to induce immune responses seen in other transplants.

More Work Ahead

The pathway to clinical trials is long, with safety and efficacy proven in the clinical domain before human patients can get involved.

Morse and her Craig team continue forging ahead with enthusiasm and high hopes.

"Realistically, we are very excited to move to clinical trial in two to three years," Morse says. "We hope these cells will have a big impact. There's currently no treatment that restores strength that would translate to functional improvements. Even improving grip strength would be a tremendous improvement for people with spinal-cord injury."

In addition to the work on dental pulp stem cells, Morse is conducting research centering on bone density in people who have sustained SCIs. When people stop walking because of an injury, the bones respond very quickly, essentially aging, and they become more susceptible to fractures. People who are eight to nine years post-injury and are not ambulatory can start to experience fractures. Morse and her team are researching the cellular signals that allow for bone weakening. The goal is to design therapies that either regenerate bone or block the process of weakening entirely.

"We need to understand the cell signals that are causing the bone loss to occur, so we can focus on target-based interventions," Morse says.

One such therapy may be the use of robotic-assisted gait therapies like those made possible by the Indego exoskeleton. The powered lower-limb exoskeleton enables people to walk and participate in over-ground gait training for bone regeneration after SCI. It is currently the subject of a Department of Defense-funded study at PEAK Center at Craig, which is Craig Hospital's adaptive health and wellness center.

Craig Center for Regenerative Research is also studying the effects of common cholesterol-lowering medication, simvastatin (statins), to prevent bone loss in the immediate months after SCI.

"There are people who think that if you have loss of significant bone, its regenerative ability is lost, and I think that's untrue based on what we're seeing," Morse says. "We think that bone retains its regenerative capacity well into old age. We need to think of innovative ways of taking advantage of that."

Caption: Leslie Morse, DO

Caption: Dental pulp stem cells harvested from discarded wisdom teeth, left, cultured under neuronal inductive conditions to express the neuronal marker Bill-tubulin, right.

Caption: Dental pulp can be extracted from discarded baby teeth.
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Author:Best, Jennifer
Publication:PN - Paraplegia News
Date:Oct 1, 2018
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